Hyperbaric Oxygen Therapy (HBOT) - bcbsks.com … · 04/10/2019 · Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen at pressures between 1.5 and 3.0 atmospheres (atm)

Hyperbaric Oxygen Therapy (HBOT) Page 1 of 85

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Title: Hyperbaric Oxygen Therapy (HBOT) Professional Institutional Original Effective Date: November 2, 1989 Original Effective Date: June 3, 2004 Revision Date(s): June 10, 2003; August 29, 2003; July 20, 2004; March 14, 2011; October 11, 2011; January 1, 2012; January 30, 2012: March 27, 2014; January 23, 2015; February 5, 2015; November 12, 2015; November 19, 2015; October 1, 2016; February 15, 2017; October 1, 2017; February 15, 2018; April 26, 2019; June 19, 2019; October 1, 2019

Revision Date(s): July 20, 2004; March 14, 2011; October 11, 2011; January 1, 2012; January 30, 2012; March 27, 2014; January 23, 2015; February 5, 2015; November 12, 2015; November 19, 2015; October 1, 2016; February 15, 2017; October 1, 2017; February 15, 2018; April 26, 2019; June 19, 2019; October 1, 2019

Current Effective Date: April 26, 2019 Current Effective Date: April 26, 2019 State and Federal mandates and health plan member contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. To verify a member's benefits, contact Blue Cross and Blue Shield of Kansas Customer Service. The BCBSKS Medical Policies contained herein are for informational purposes and apply only to members who have health insurance through BCBSKS or who are covered by a self-insured group plan administered by BCBSKS. Medical Policy for FEP members is subject to FEP medical policy which may differ from BCBSKS Medical Policy.

The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents of Blue Cross and Blue Shield of Kansas and are solely responsible for diagnosis, treatment and medical advice. If your patient is covered under a different Blue Cross and Blue Shield plan, please refer to the Medical Policies of that plan.

Populations Interventions Comparators Outcomes Individuals: • With wounds, burns,

or infections

Interventions of interest are: • Topical hyperbaric oxygen

therapy

Comparators of interest are: • Dressings • Débridement • Medication

Relevant outcomes include: • Overall survival • Symptoms • Change in disease status • Functional outcomes

Individuals: • With chronic diabetic

ulcers

Interventions of interest are: • Systemic hyperbaric

oxygen therapy

Comparators of interest are: • Standard wound care • Advanced wound therapy

Relevant outcomes include: • Symptoms • Change in disease status

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Populations Interventions Comparators Outcomes Individuals: • With carbon

monoxide poisoning


oxygen therapy

Comparators of interest are: • Breathing oxygen at

standard pressure

Relevant outcomes include: • Overall survival • Symptoms

Individuals: • With radionecrosis,

osteoradionecrosis, and treatment of irradiated jaw


oxygen therapy

Comparators of interest are: • Débridement • Medication


Individuals: • With chromic

refractory osteomyelitis


oxygen therapy

Comparators of interest are: • Medication • Surgical therapy


Individuals: • With acute thermal

burns


oxygen therapy

Comparators of interest are: • Cooling therapy • Medication

Relevant outcomes include: • Overall survival • Symptoms • Change in disease status

Individuals: • With acute surgical

and traumatic wounds


oxygen therapy

Comparators of interest are: • Dressings • Débridement • Medication


Individuals: • With

bisphosphonate-related osteonecrosis of the jaw


oxygen therapy



Individuals: • With necrotizing soft

tissue infections


oxygen therapy



Individuals: • With acute coronary

syndrome


oxygen therapy



Individuals: • With acute ischemic

stroke


oxygen therapy

Comparators of interest are: • Tissue plasminogen

activator • Endovascular procedure


Individuals: • With motor

dysfunction associated with stroke


oxygen therapy

Comparators of interest are: • Physical therapy

Relevant outcomes include: • Symptoms • Functional outcomes

Individuals: • With Bell's palsy


oxygen therapy

Comparators of interest are: • Self-care (eg, artificial

tears, eyepatch) • Medication

Relevant outcomes include: • Symptoms • Change in disease status • Functional outcomes

Individuals: • With traumatic brain

injury


oxygen therapy

Comparators of interest are: • Medication • Surgical therapy • Rehabilitation





Populations Interventions Comparators Outcomes Individuals: • With inflammatory

bowel disease


oxygen therapy



Individuals: • With idiopathic

sudden sensorineural hearing loss


oxygen therapy



Individuals: • With delayed-onset

muscle soreness


oxygen therapy

Comparators of interest are: • Conservative care (eg,

massage) • Medication


Individuals: • With autism

spectrum disorder


oxygen therapy

Comparators of interest are: • Behavioral therapy • Medication


Individuals: • With cerebral palsy


oxygen therapy

Comparators of interest are: • Physical therapy • Medication


Individuals: • With vascular

dementia


oxygen therapy

Comparators of interest are: • Rehabilitation • Medication


Individuals: • With radiotherapy

adverse effects


oxygen therapy

Comparators of interest are: • Medication


Individuals: • With idiopathic

femoral neck necrosis


oxygen therapy

Comparators of interest are: • Physical therapy • Medication • Surgical therapy


Individuals: • With migraine


oxygen therapy



Individuals: • With herpes zoster


oxygen therapy



Individuals: • With fibromyalgia


oxygen therapy



Individuals: • With multiple

sclerosis


oxygen therapy

Comparators of interest are: • Behavioral therapy • Medication


Individuals: • With cancer who are

undergoing chemotherapy


oxygen therapy

Comparators of interest are: • Chemotherapy without

hyperbaric oxygen therapy

Relevant outcomes include: • Overall survival • Change in disease status




DESCRIPTION Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen at pressures between 1.5 and 3.0 atmospheres (atm). Hyperbaric oxygen therapy is generally applied systemically with the patient inside a hyperbaric chamber. It can also be applied topically; that is, the body part to be treated is isolated, eg, in an inflatable bag and exposed to pure oxygen. HBOT has been investigated for various conditions that have potential to respond to increased oxygen delivery to the tissues.

OBJECTIVE The objective of this policy is to determine whether the use of topical or systemic hyperbaric oxygen pressurization for a variety of indications improves net health outcomes.

BACKGROUND Hyperbaric Oxygen Therapy Hyperbaric oxygen therapy (HBOT) is a technique of delivering higher pressures of oxygen to the tissues. Two methods of administration are available: systemic and topical. Systemic HBOT In systemic or large chamber hyperbaric oxygen, the patient is entirely enclosed in a pressure chamber and breathes oxygen at a pressure greater than 1 atmosphere (the pressure of oxygen at sea level). Thus, this technique relies on systemic circulation to deliver highly oxygenated blood to the target site, typically a wound. Systemic hyperbaric oxygen therapy can be used to treat systemic illness, such as air or gas embolism, carbon monoxide poisoning, or clostridial gas gangrene. Treatment may be carried out either in a monoplace chamber pressurized with pure oxygen or in a larger, multiplace chamber pressurized with compressed air, in which case the patient receives pure oxygen by mask, head tent, or endotracheal tube. Topical HBOT Topical hyperbaric oxygen therapy is a technique of delivering 100% oxygen directly to an open, moist wound at a pressure slightly higher than atmospheric pressure. It is hypothesized that the high concentrations of oxygen diffuse directly into the wound to increase the local cellular oxygen tension, which in turn promotes wound healing. Topical hyperbaric oxygen devices consist of an appliance to enclose the wound area (frequently an extremity) and a source of oxygen; conventional oxygen tanks may be used. The appliances may be disposable and may be used without supervision in the home by well-trained patients. Topical hyperbaric oxygen therapy has been investigated as a treatment of skin ulcerations resulting from diabetes, venous stasis, postsurgical infection, gangrenous lesion, decubitus ulcers, amputations, skin graft, burns, or frostbite.




Adverse Events HBOT is a generally safe therapy, with an estimated adverse side effect rate of 0.4%.1 Adverse events may occur either from pressure effects or the oxygen. The pressure effect (barotrauma) may affect any closed air-filled cavity such as ears, sinus, teeth, and lungs. Pain and/or swelling may occur at these sites as pressure increases during the procedure, and decreases as the procedure is ending. Oxygen toxicity may affect the pulmonary, neurologic, or ophthalmologic systems. Pulmonary symptoms include a mild cough, substernal burning, and dyspnea. Neurologic effects include tunnel vision, tinnitus, nausea, and dizziness. Ophthalmologic effects include retinopathy in neonates, cataract formation, and transient myopic vision changes. Note that this policy does not address topical oxygen therapy in the absence of pressurization.

REGULATORY STATUS Since 1979, the Food and Drug Administration (FDA) has cleared multiple topical and systemic hyperbaric oxygen administration devices through the 510(k) pathway. In 2013, FDA published a statement warning that non-FDA approved uses of HBOT may endanger the health of patients.2 If patients mistakenly believe that HBOT devices have been proven safe for uses not cleared by FDA, they may delay or forgo proven medical therapies.




POLICY A. Systemic hyperbaric oxygen pressurization may be considered medically

necessary in the treatment of any of the following conditions: 1. Acute traumatic ischemia (eg, crush injuries, reperfusion injury, compartment

syndrome); OR 2. Carbon monoxide poisoning, acute; OR 3. Cyanide poisoning, acute; OR 4. Non-healing diabetic wounds of the lower extremities in patients who meet the

following criteria: a) Patient has type 1 or type 2 diabetes and has a lower extremity wound

due to diabetes; b) Patient has a wound classified as Wagner grade 3 or higher (see Policy

Guidelines); and c) Patient has no measurable signs of healing after 30 days of an adequate

course of standard wound therapy; OR 5. Chronic refractory osteomyelitis; OR 6. Decompression sickness; OR 7. Soft tissue radiation necrosis; OR 8. Gas embolism, acute; OR 9. Gas gangrene (ie, clostridial myonecrosis); OR 10. Pre and post treatment for individuals undergoing dental surgery (non-implant

related) of an irradiated jaw; OR 11. Profound anemia with exceptional blood loss: only when blood transfusion is

impossible or must be delayed.

B. Hyperbaric oxygen pressurization is considered experimental / investigational in all other situations including, but not limited to, the treatment of the following conditions: 1. Acute osteomyelitis; 2. Acute surgical and traumatic wounds; 3. Spinal cord injury; 4. Traumatic brain injury; 5. Inflammatory bowel disease (Crohn's disease or ulcerative colitis); 6. Brown recluse spider bites; 7. Bone grafts; 8. Carbon tetrachloride poisoning, acute; 9. Cerebrovascular disease, acute (thrombotic or embolic) or chronic; 10. Fracture healing; 11. Hydrogen sulfide poisoning; 12. Intra-abdominal and intracranial abscesses; 13. Lepromatous leprosy; 14. Meningitis; 15. Pseudomembranous colitis (antimicrobial agent-induced colitis); 16. Radiation myelitis;




17. Sickle cell crisis and/or hematuria; 18. Demyelinating diseases, eg, multiple sclerosis, amyotrophic lateral sclerosis; 19. Retinopathy, adjunct to scleral buckling procedures in patients with sickle cell

peripheral retinopathy and retinal detachment; 20. Pyoderma gangrenosum; 21. Acute coronary syndromes and as an adjunct to coronary interventions,

including, but not limited to, percutaneous coronary interventions and cardiopulmonary bypass;

22. Idiopathic sudden sensorineural hearing loss; 23. Refractory mycoses: mucormycosis, actinomycosis, conidiobolus coronato; 24. Cerebral edema, acute; 25. Migraine; 26. In vitro fertilization; 27. Cerebral palsy; 28. Tumor sensitization for cancer treatments, including, but not limited to,

radiotherapy or chemotherapy; 29. Delayed onset muscle soreness; 30. Idiopathic femoral neck necrosis; 31. Chronic arm lymphedema following radiotherapy for cancer; 32. Radiation-induced injury in the head and neck (except as noted in Item A10

above); 33. early treatment (beginning at completion of radiotherapy) to reduce adverse

effects of radiotherapy; 34. autism spectrum disorders; 35. bisphosphonate-related osteonecrosis of the jaw; 36. acute ischemic stroke; 37. motor dysfunction associated with stroke; 38. herpes zoster; 39. vascular dementia; 40. fibromyalgia; 41. Compromised skin grafts or flaps; 42. Necrotizing soft tissue infections; 43. Acute thermal burns; 44. Chronic wounds, other than those in patients with diabetes who meet the

criteria specified in Item A4 above); 45. Acute arterial peripheral insufficiency; 46. Mental illness (ie, posttraumatic stress disorder, generalized anxiety disorder,

or depression); 47. Bell's palsy; and 48. Central retinal artery occlusion.

C. Topical hyperbaric oxygen therapy is considered experimental / investigational.




Policy Guidelines Topical Hyperbaric Oxygen This policy addresses topical hyperbaric oxygen therapy but not topical oxygen wound care. Topical hyperbaric oxygen may be performed in the office, clinic, or may be self-administered by the patient in the home. Typically, the therapy is offered for 90 minutes per day for 4 consecutive days. After a 3-day break, the cycle is repeated. The regimen may last for 8 to 10 weeks. Systemic Hyperbaric Oxygen The Wagner classification system of wounds is defined as follows: grade 0, no open lesion; grade 1, superficial ulcer without penetration to deeper layers; grade 2, ulcer penetrates to tendon, bone, or joint; grade 3, lesion has penetrated deeper than grade 2 and there is abscess, osteomyelitis, pyarthrosis, plantar space abscess, or infection of the tendon and tendon sheaths; grade 4, wet or dry gangrene in the toes or forefoot; grade 5, gangrene involves the whole foot or such a percentage that no local procedures are possible and amputation (at least at the below the knee level) is indicated. Below are suggestions from the Undersea and Hyperbaric Medical Society’s (UHMS) 2014 Hyperbaric Oxygen Therapy Committee report on utilization of hyperbaric oxygen therapy (HBOT) (13th edition): 1. Crush injury, compartment syndrome, and other acute traumatic ischemias. 2. Decompression sickness. 3. Air or Gas embolism. 4. Carbon monoxide poisoning and carbon monoxide poisoning complicated by

cyanide poisoning. 5. Gas gangrene (ie, clostridial myonecrosis and myonecrosis). 6. Severe anemia. 7. Refractory osteomyelitis. 8. Arterial insufficiencies. 9. Intracranial abscess. 10. Necrotizing soft tissue infections. 11. Delayed radiation injury (soft tissue and bony necrosis). 12. Compromised grafts and flaps. 13. Acute thermal burn injury. 14. Idiopathic sudden sensorineural hearing loss. Treatment duration recommendations: 1. Enhancement of healing in problem wounds: Treatments are performed for 90 to

120 minutes. The initial treatment schedule depends on the severity of disease. More serious conditions may require twice daily treatments; when stabilized, this




can decrease to once daily. Utilization review is required after the initial 30 days of treatment and at least once every additional 30 days.

2. Crush injury, compartment syndrome, and other acute traumatic ischemias: a. Reperfusion injury: 1 treatment. b. Crush injury: 8-12 treatments (three times per day for 2 days, then twice a

day for 2 days, and daily for 2 days). c. Compartment syndrome: 3-4 treatments (twice a day for 1 day and one

treatment on day 2). 3. Decompression sickness: The majority of cases respond to a single treatment.

Patients with residual defects after the initial session should receive additional treatments until they achieve clinical stability (generally no more than 5-10 treatments). Utilization review is recommended after 10 treatments.

4. Gas embolism, acute: It is recommended that treatments continue until there is no additional improvement; this typically occurs after 1-2 treatments but occasionally up to 5-10. Utilization review is recommended after 10 treatments.

5. Acute carbon monoxide poisoning and carbon monoxide poisoning complicated by cyanide poisoning: Some patients improve after a single treatment. Patients who fail to demonstrate a full recovery should receive additional treatments. In patients with persistent neurologic dysfunction after the initial treatment, further treatment can occur within 6-8 hours and can be continued once or twice daily until there is no additional improvement in cognitive function. Utilization review is mandatory after the fifth treatment.

6. Soft-tissue radiation necrosis (eg, radiation enteritis, cystitis, proctitis) and osteoradionecrosis: Most treatment courses for radiation injury will be 30-60 treatments (once daily for 90 to 120 minutes). Utilization review is recommended after 60 treatments.

7. Mandibular osteoradionecrosis: The initial course of treatment for patients with stage I osteoradionecrosis is 30 sessions, followed by only minor bony debridement. If response is adequate, an additional 10 treatments are given. If patients are not responding they are considered stage II and they receive more extensive surgical debridement, followed by 10 additional treatments. Patients who present as stage III patients receive 30 treatments followed by mandibular segmental resection and then an additional 10 treatments.

8. Gas gangrene (ie, clostridial myonecrosis): Recommended are three 90-minute treatments during the first 24 hours and then 2 treatments per day for the next 2-5 days, depending on the patient’s initial response. Utilization review is indicated after 10 treatments.

9. Severe anemia: HBOT can be considered for severe anemia when patients cannot receive blood products due to medical, religious, or strong personal preference reasons. Treatment can occur for periods of up to 3 or 4 hours 3 to 4 times a day if patients receive intra-treatment air breaks. HBOT treatment should be continued with taper of both time and frequency until red blood cells have been satisfactorily replaced by patient regeneration or the patient can undergo transfusion.




10. Chronic refractory osteomyelitis: No recommendations were made for the total number of treatments required. For patients who respond to initial treatment with antibiotics, surgical debridement, and HBOT, therapy should be continued for approximately 4-6 weeks. Utilization review is indicated after 30-40 sessions.

RATIONALE Updated literature reviews were conducted most recently through October 29, 2018. Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function¾including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms. To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice. The original evidence review on systemic hyperbaric oxygen therapy [HBOT] was based entirely on the 1996 guidelines published by the Undersea and Hyperbaric Medical Society; it was subsequently revised in 1999 based on 3 TEC Assessments.3,4,5,The TEC Assessments had conclusions similar to the Undersea and Hyperbaric Medical Society, except, in contrast to the Society guidelines, TEC stated that there was insufficient evidence to conclude that HBOT improved the net health outcome for compromised skin grafts, acute thermal burns, chronic refractory osteomyelitis, necrotizing soft tissue infections, and brown recluse spider bites. Evidence for a majority of the indications consists of Cochrane systematic reviews, which focus on summarizing RCTs, and when possible, conducting pooled analyses of results. Topical Hyperbaric Oxygen Therapy for Wounds, Burns, or Infections Clinical Context and Therapy Purpose The purpose of topical HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with wounds, burns, or infections. The question addressed in this evidence review is: Does the use of topical hyperbaric oxygen as a treatment for wounds, burns, or infections improve net health outcomes? The following PICOTS were used to select literature to inform this review.

https://www.evidencepositioningsystem.com/BCBSA/html/_w_ce3a030c593696e527c5de33ad90941b76e892e28c1fa7ee/#reference-3






Patients The relevant population of interest is individuals with wounds, burns, or infections. Interventions The therapy being considered is topical HBOT. Comparators Comparators of interest include dressings, débridement, and medication. Medications prescribed may include topical antibiotics and antiseptics. Pain and anxiety management medication may also be used. Topical HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival, symptoms, change in disease status, and functional outcomes. Timing Based on the site and severity of the wound, burn, or infection, patients may require prolonged physical and occupational support to evaluate symptoms. Additionally, the existing evidence on the use of topical HBOT involves studies that treat patients for 12 weeks, but information on follow-up was limited. Therefore, follow-up should be determined based on the site and severity of the wound, burn, or infection and can range from months to a year after starting treatment. Setting Patients with wounds, burns, or infections are actively managed by emergency care providers, dermatologists, wound care specialists, and primary care providers in a clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:

a. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c. To assess longer term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Studies with duplicative or overlapping populations were excluded. de Smet (2017) et al conducted a systematic review of various oxygen therapies (oxygen dressing therapy, topical oxygen therapy, HBOT, inspired oxygen therapy).6, Three RCTs evaluating topical oxygen therapy for chronic wound healing were identified (see Table 1). One RCT (N=100) administered treatment for 20 minutes 3 times per day for 12 days to the treatment group and standard care to the control group. The number of patients experiencing complete wound healing, defined as complete epithelialization of the wound without drainage, was 16 in the experimental group and 1 in the control group (p<0.001). Two of the RCTs, which had overlapping populations with refractory venous ulcers (n=83 in one and n=132 in the other) administered treatment for 180 minutes 2 times per day for 12 weeks to the treatment group and conventional compression dressing to the control group. In all trials, patients in the treatment





group experienced significantly higher proportions of healed ulcers and significantly faster healing times. A small RCT reported by Leslie (1988) not included in the systematic review evaluated 28 patients with diabetic foot ulcers who were assigned to topical HBOT plus standard wound care or standard wound care alone.7, Changes in ulcer size and depth did not differ between the 2 groups following 2 weeks of treatment. Table 1. Systematic Reviews of Trials Assessing Topical Hyperbaric Oxygen for Wounds

Study (Year)

Literature Search

Studies Participants N (Range)

Design Results

de Smet et al

(2017)6,

Feb 2016 3 · Stage II-IV sacral or ischial pressure ulcers

(1 RCT) · Refractory venous

ulcers (2 RCTs)

315a (83-132)

RCT · Results not pooled · In all trials, patients in

the treatment group experienced significantly

higher wound healing rates RCT: randomized controlled trial. a Two of the trials had overlapping populations, so there were not 315 unique patients. Section Summary: Topical Hyperbaric Oxygen for Wounds, Burns, or Infections A systematic review identified 3 RCTs on the use of topical HBOT for chronic wound healing. The results showed topical oxygen therapy improved wound healing, but there was heterogeneity in the trial populations and treatment regimens. There is a small RCT on topical HBOT for diabetic foot ulcers; it showed no differences in outcomes between the treatment and control group. No controlled studies on topical HBOT for patients with burns or infections were identified. The data are insufficient to draw conclusions about the effect on the net health outcome. Systemic Hyperbaric Oxygen Therapy for Chronic Diabetic Ulcers Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with chronic diabetic ulcers. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for chronic diabetic ulcers improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with chronic diabetic ulcers. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include standard wound care and advanced wound therapy. Standard wound care can include offloading of the wound with appropriate therapeutics, dressings, debridement antibiotic therapy, and blood glucose control. Advanced wound therapy can include the application of recombinant growth factors and wound coverage with heterogeneic dressings. Systemic HBOT may be used as an adjunct to these comparators. Outcomes






The general outcomes of interest are symptoms and change in disease status. Timing The existing literature evaluating systemic HBOT as a treatment for chronic diabetic ulcers has varying lengths of follow-up, ranging from none to 22 months. While studies included in the systematic reviews described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with chronic diabetic ulcers are managed by surgeons, wound care specialists, podiatrists and primary care providers in a clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. Systematic Reviews A Cochrane review of RCTs on HBOT for chronic wounds was published by Kranke et al in 2015 (see Table 2).8, Reviewers identified 12 RCTs (total N=577 participants) comparing the effect of HBOT on chronic wound healing with an alternative treatment approach that did not use HBOT. Ten of the 12 trials evaluated HBOT in patients with diabetes (N=531). The trials were assessed as moderate quality using the GRADE system. HBOT regimens varied across studies, ranging from 3.0 atmospheres absolute (ATA) for 45 minutes to 2.2 ATA for 120 minutes. In a pooled analysis of 5 trials, a significantly higher proportion of ulcers had healed at the end of treatment (ie, 6 weeks) in the group receiving HBOT than in the group not receiving HBOT, but there was no statistically significant difference in the risk of major amputations between groups. A 2016 systematic review by Elraiyah et al evaluated adjunctive therapies (HBOT, arterial pumps, and pharmacologic agents) used to treat diabetic foot ulcers (see Table 2).9, RCTs and nonrandomized cohort studies were included. The RCTs were rated as low-to-moderate quality using the GRADE system. A pooled analysis of 6 RCTs found a significantly higher healing rate and a significantly lower major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10 to 0.89) with HBOT than with control. Table 2. Systematic Reviews of Trials Assessing HBOT for Chronic Diabetic Foot Ulcers

Study (Year)

Literature Search

Studies Participants N Design Results

Kranke et al (2015)8,

Feb 2015 12 Patients with chronic wounds associated with venous or arterial disease,

577 RCTs · 10 of 12 trials focused on patients with diabetic foot ulcers (n=531) · Pooled analysis of 5 of 10 trials (n=205) reported higher heal rates







Study (Year)

Literature Search


diabetes, or external pressure

with HBOT (RR=2.3; 95% CI, 1.2 to 4.6) and no difference in amputation risk (RR=0.4; 95% CI, 0.1 to 2.2)

Elraiyah et al (2016)9,

Oct 2011 18 Patients with diabetic foot ulcers

1526 RCTs, cohort

· 16 of 18 trials included HBOT as a treatment option and 6 of those were RCTs · Pooled analysis of the 6 RCTs (n=340) reported higher heal rate with HBOT (OR=14.3; 95% CI, 7.1 to 28.7) and lower amputation risk (OR=0.3; 95% CI, 0.1 to 0.9)

HBOT: hyperbaric oxygen therapy; OR: odds ratio; RCT: randomized controlled trial; RR: relative risk. Section Summary: Chronic Diabetic Ulcers Multiple RCTs and 2 systematic reviews have been published. Seven RCTs were common in the 2 systematic reviews. Pooled analyses of RCTs found significantly higher wound healing rates with HBOT than with control conditions. One of the 2 meta-analyses found that HBOT was associated with a significantly lower rate of major amputation. Systemic Hyperbaric Oxygen Therapy for Carbon Monoxide Poisoning Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with carbon monoxide poisoning. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for carbon monoxide poisoning improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with carbon monoxide poisoning. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include breathing oxygen at standard pressure and other supportive measures such as a ventilator. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival and symptoms. Timing The existing literature evaluating systemic HBOT as a treatment for carbon monoxide poisoning has varying lengths of follow-up. In the systematic review described below all reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy.





Setting Patients with carbon monoxide poisoning are managed in the emergency care setting by emergency medicine physicians. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded.

A 2011 Cochrane review by Buckley et al included 6 RCTs evaluating HBOT for carbon monoxide poisoning (see Table 3).10, Four of the 6 trials were assessed as having a high risk of bias due to nonblinding of treatment allocation. The trials had substantial methodologic and statistical heterogeneity. The outcome of interest was dichotomous, presence or absence of signs or symptoms indicative of neurologic injury at 4 to 6 weeks after study inclusion. Two of the 6 RCTs found that HBOT reduced the likelihood of neurologic sequelae at 1 month and 4 others did not find a significant effect. A pooled analysis of the 6 trials did not find a significant effect of HBOT on neurologic injury. Reviewers concluded that there was insufficient evidence to determine whether HBOT reduces the risk of adverse neurologic outcomes after carbon monoxide poisoning. Quality of the evidence was deemed very low, using the GRADE system. Table 3. Systematic Reviews of Trials Assessing HBOT for Carbon Monoxide Poisoning

Study (Year)

Literature Search


Buckleyet al (2011)10,

Jun 2010 6 Nonpregnant adults with acute carbon monoxide poisoning

1361 RCTs · Studies extremely heterogeneous in: severity of CO poisoning, HBOT regimens, and comparators · Pooled analyses of 6 trials (N=1361) reported no statistical difference in neurologic deficits between treatment groups (OR=0.78; 95% CI, 0.54 to 1.12)

CI: confidence interval; CO: carbon monoxide; HBOT: hyperbaric oxygen therapy; OR: odds ratio; RCT: randomized controlled trial. Section Summary: Carbon Monoxide Poisoning A Cochrane review identified 6 RCTs, the majority of which did not find a significant effect of HBOT on health outcomes. A pooled analysis of the RCT data did not find a significant effect of HBOT on neurologic injuries and the quality of the evidence was considered very low.






Systemic Hyperbaric Oxygen Therapy for Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with radionecrosis, osteoradionecrosis, and treatment of irradiated jaw. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for radionecrosis, osteoradionecrosis and treatment of irradiated jaw improve net health outcomes. The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with radionecrosis, osteoradionecrosis, and treatment of irradiated jaw. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include débridement and medication. Medications prescribed for radionecrosis may include corticosteroids and anticoagulants. For osteoradionecrosis, medications include vasodilators. Medication for the treatment of irradiated jaw can include antibiotics. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and change in disease status. Timing The existing literature evaluating systemic HBOT as a treatment for radionecrosis, osteoradionecrosis, and treatment of irradiated jaw has varying lengths of follow-up, ranging from 3 weeks to 18 months. In the systematic reviews described below, nearly all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with radionecrosis, osteoradionecrosis, and treatment of irradiated jaw are managed by radiation oncologists, orthopedic surgeons and oral maxillofacial surgeons potentially in both inpatient and outpatient clinical settings. Study Selection Criteria Methodologically credible studies were selected using the following principles:







Studies with duplicative or overlapping populations were excluded. Bennett (2016) et al published a Cochrane review on HBOT for late radiation tissue injury (see Table 4).11, Reviewers identified 14 RCTs. There was a moderate level of evidence for 2 pooled analyses. In a pooled analysis of 3 studies, a significantly higher proportion of patients with osteoradionecrosis achieved complete mucosal cover after HBOT compared with control treatments, and in a pooled analysis of 2 trials, a significantly lower risk of wound dehiscence after surgery to repair mandibular osteoradionecrosis with HBOT than with control treatments was reported. A single trial found a significantly higher likelihood of successful healing with HBOT than with antibiotics for tooth extraction in irradiated jaws (absolute risk reduction, 25%; p=0.02). There were insufficient data to conduct meta-analyses on other outcomes. Borab (2017) et al published a systematic review focusing on the use of HBOT to treat the subgroup of patients with late radiation tissue injury had skin necrosis (see Table 4).12, Reviewers identified 8 studies, including a large observational cohort and several case series. No RCTs were identified. The risk of bias was high due to the design of the included studies. The studies reported improved healing, though, without a comparator, interpretation of the results is limited. Ravi (2017) et al published a systematic review on the use of HBOT to treat patients who had received radiotherapy for head and neck cancer.13, Ten prospective case series and comparative studies were identified. Qualitative summaries of outcomes were provided, but pooled analyses were not performed. Outcomes of interest included osteonecrosis and dental implant survival (see Table 4). Other outcomes of interest included salivary gland function and quality of life, which are discussed in the Radiotherapy Adverse Events section. Table 4. Systematic Reviews of Studies Assessing HBOT for Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw

Study (Year)

Literature Search


Bennett et al (2016)11,

Dec 2015 14 Patients with late radiation tissue injury (including necrosis) and patients treated with large-dose radiotherapy likely to induce early necrosis

753 RCTs · Pooled analyses of 3 trials of patients with osteoradionecrosis (n=246) found a higher rate of complete mucosal cover after HBOT vs control (RR=1.3; 95% CI, 1.1 to 1.5) · Pooled analyses of 2 trials (n=264) found a lower risk of wound dehiscence following surgery to repair mandibular osteoradionecrosis in patients treated with HBOT vs control (RR=4.2; 95% CI, 1.1 to 16.8)

Borab et al (2017)12,

May 2016 8 Patients with radiation-induced skin necrosis

720 Observational cohort and case series

· Adding across the studies, 80% reported complete healing and 86% reported symptom improvement · Studies had no comparators

Ravi et al (2017)13,

Dec 2016 10 Patients who received

375 Prospective case series and

· Osteonecrosis prevention: 1 case series and 1 comparative study










Study (Year)

Literature Search


radiotherapy for head and neck cancer

prospective comparative studies

(n=77) reported low osteonecrosis rates with HBOT · Dental implant survival: 1 case series and 2 comparative studies (n=122) report mixed results, with 2 studies finding implant survival improved with HBOT and anotherfinding no difference in survival

CI: confidence interval; HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial; RR: relative risk. Section Summary: Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw A Cochrane review of RCTs found that HBOT improved some radionecrosis and osteoradionecrosis outcomes and resulted in better outcomes before tooth extraction in an irradiated jaw. Observational studies focused on skin necrosis and reported high rates of healing with HBOT, though with no comparators, interpretation of results is limited. Prospective observational studies using HBOT for treatment on patients with head and neck cancer receiving HBOT, have reported low osteonecrosis rates and inconsistent results for dental implant survival. The number of RCTs evaluating HBOT for these indications, especially in irradiated jaws, is limited. Systemic Hyperbaric Oxygen Therapy for Chronic Refractory Osteomyelitis Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with chronic refractory osteomyelitis. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for chronic refractory osteomyelitis improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with chronic refractory osteomyelitis. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication and surgical therapy. Medications prescribed for chronic refractory osteomyelitis may include intravenous antibiotics. Surgery can include débridement. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and change in disease status.




Timing The existing literature evaluating systemic HBOT as a treatment for chronic refractory osteomyelitis report follow-up times ranging from 34 to 60 months, suggesting that extensive follow-up up to or more than five years is considered necessary to demonstrate efficacy. Setting Patients with chronic refractory osteomyelitis are managed by orthopedic surgeons, wound specialists, and primary care providers. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. No prospective clinical trials on chronic or refractory osteomyelitis were identified in literature searches. The evidence for the use of HBOT in chronic osteomyelitis has been primarily based on case series. Among the larger case series, Maynor et al (1998) reviewed the records of all patients with chronic osteomyelitis of the tibia seen at a single institution.14, Follow-up data were available on 34 patients who had received a mean of 35 adjunctive HBOT sessions (range, 6-99 sessions). Of the 26 patients with at least 24 months of follow-up after treatment, 81% (21/26) remained drainage-free. At 60 months of follow-up, 80% (12/15), and at 84 months, 63% (5/8) remained drainage-free. Davis et al (1986) reviewed outcomes for 38 patients with chronic refractory osteomyelitis treated at another U.S. institution.15, Patients received HBOT until the bone was fully recovered with healthy vascular tissue; this resulted in a mean of 48 daily treatments (range, 8-103 treatments). After a mean posttreatment follow-up of 34 months, 34 (89%) of 38 patients remained clinically free of infection (ie, drainage-free and no tenderness, pain, or cellulitis). Success rates from several smaller case series (N range, 13-15 patients), all conducted in Taiwan (1998-2000), ranged from 79% to 92%.16,17,18, A high percentage of refractory patients in these series had successful outcomes. Section Summary: Chronic Refractory Osteomyelitis Only case series data are available; no RCTs or comparative nonrandomized trials were identified. Case series tended to find high rates of successful outcomes in patients with chronic refractory osteomyelitis treated with HBOT. However, controlled studies are needed to determine conclusively that HBOT improves health outcomes in patients with chronic refractory osteomyelitis compared with other interventions.









Systemic Hyperbaric Oxygen Therapy for Acute Thermal Burns Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with acute thermal burns. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for acute thermal burns improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with acute thermal burns. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include cooling therapy and medication. Medications prescribed for acute thermal burns may include antibiotics. Pain and anxiety medication may also be used. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival, symptoms, and change in disease status. Timing The existing literature evaluating systemic HBOT as a treatment for acute thermal burns does not report follow-up time. However, given that patients may require prolonged occupational and physical therapy based on the site and severity of the acute thermal burn, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with acute thermal burns are managed by burn specialists and surgeons in an inpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. In 2004, a Cochrane review assessed HBOT for thermal burns (see Table 5).19, Two RCTs were identified, published in 1974 and 1997. Sample sizes were 16 and 125. Both trials were judged by reviewers to have poor methodologic quality. Reviewers concluded that the evidence was





insufficient to permit conclusions on whether HBOT improves health outcomes in patients with acute thermal burns. No additional trials were identified when an updated literature search was conducted in 2009 (the 2004 publication date continues to be used). Table 5. Systematic Reviews of Trials Assessing HBOT for Acute Thermal Burns

Study (Year)

Literature Search


Villanueva et al (2009)19,

Jun 2009

5 Patients with thermal injuries to the epidermis, subcutaneous tissues, vessels, nerve, tendons, or bone

141 RCTs · 1 trial (N=125) reported no difference in length of stay, mortality, or number of surgeries between HBOT and control groups · 1 trial (N=16) reported shorter healing times (19.7 days vs 43.8 days; p<0.001) with HBOT vs control, and an RR for failed graft without HBOT of 2.0 (95% CI 0.5 to 8.0)

CI: confidence interval; HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial; RR: relative risk. Section Summary: Acute Thermal Burns A Cochrane review identified 2 RCTs on HBOT for thermal burns. Both were judged to have poor methodologic quality. There is insufficient evidence from well-conducted controlled studies to permit conclusions on the impact of HBOT on health outcomes in patients with acute thermal burns. Systemic Hyperbaric Oxygen Therapy for Acute Surgical and Traumatic Wounds Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with acute surgical and traumatic wounds. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for acute surgical and traumatic wounds improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with acute surgical and traumatic wounds. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include dressings, débridement, and medication. Medications prescribed for acute surgical and traumatic wounds may include antibiotics and pain management. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival, symptoms, and change in disease status.





Timing The existing literature evaluating systemic HBOT as a treatment for acute surgical and traumatic wounds has varying lengths of follow-up, though many had short follow-up period of 6 to 7 days. Depending on the severity of the wounds, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with acute surgical and traumatic wounds are actively managed by emergency care providers and surgeons in an inpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. In 2013, a Cochrane review of RCTs on HBOT for acute surgical and traumatic wounds was published by Eskes et al (see Table 6).20, HBOT was administered at pressures above 1 atmosphere (atm). To be included, studies had to compare HBOT with a different intervention or compare 2 HBOT regimens; also, studies had to measure wound healing objectively. Four RCTs met reviewers’ inclusion criteria. Trials ranged in size from 10 to 135 participants. Due to differences among trials regarding patient population, comparison intervention, and outcome measurement, results could not be pooled. The primary outcome examined by Cochrane reviewers (wound healing) was not reported in either of the 2 trials comparing HBOT with usual care and was not reported in the trial comparing HBOT with dexamethasone or heparin. Complete wound healing was reported in the RCT comparing active HBOT with sham HBOT. In this study (N=36), there was a statistically higher rate of wound healing in the group, though the time point for outcome measurement in this trial was unclear. Also, there was no statistically significant difference between groups in the mean time to wound healing. A 2014 systematic review of studies on HBOT for acute wounds, published by Dauwe et al, included RCTs and controlled nonrandomized studies (see Table 6).21, Reviewers included 8 studies, with sample sizes ranging from 5 to 125 patients. Four studies were randomized, three were prospective observational studies, and one was a retrospective observational study. As in the Eskes systematic review, data were not pooled. Reviewers noted that 7 of the 8 studies reported statistically significant findings for their primary end points, but the end points differed among studies (eg, graft survival, hospital length of stay, wound size). Moreover, the studies were heterogeneous regarding treatment regimens, patient indications (eg, burns, facelifts), and study designs making it difficult to draw conclusions about the effect of HBOT on acute wound treatment.






Table 6. Systematic Reviews of Trials Assessing HBOT for Acute Surgical and Traumatic Wounds Study (Year)

Literature Search


Eskes et al (2013)20,

Aug 2013 4 Patients with acute wounds (skin injuries occurring due to surgery or trauma)

229 RCTs · 3 of 4 trials did not include wound healing as an outcome measure · A small trial (N=36) reported patients receiving HBOT had significantly higher wound healing rate vs sham; however, no difference in time to healing

Dauwe et al (2014)21,

Oct 2012 8 Patients with acute wounds, grafts, and flaps

256 RCTs and nonrandomized studies

· HBOT may augment healing of acute wounds · Not indicated for routine wound management

HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial. Section Summary: Acute Surgical and Traumatic Wounds Two systematic reviews identified 4 RCTs; one of the reviews also included nonrandomized studies. Heterogeneity among studies (eg, in patient population, treatment regimen, comparison group, outcomes) prevented pooling of study findings and limited the ability to draw conclusions about the impact of HBOT on health outcomes in patients with acute and traumatic wounds. Additional evidence from high-quality RCTs is needed. Systemic Hyperbaric Oxygen Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with bisphosphonate-related osteonecrosis of the jaw. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for bisphosphonate-related osteonecrosis of the jaw improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with bisphosphonate-related osteonecrosis of the jaw. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication and surgical therapy. Medications prescribed may consist of systemic antibiotics and systemic or topical antifungals. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms, and change in disease status.






Timing The existing literature evaluating systemic HBOT as a treatment for bisphosphonate-related osteonecrosis of the jaw analyzed follow-up to 18 months. Though follow-up to 3-month showed initial benefits, the RCT reported below recommended longer term follow-up to analyze outcomes compared with standard of care. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy and superiority to comparators. Setting Patients with bisphosphonate-related osteonecrosis of the jaw are managed by surgeons, dentists, and oral maxillofacial surgeons in both inpatient and outpatient clinical settings. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. An unblinded RCT by Freiberger et al (2012) evaluated the use of HBOT as an adjunct therapy for patients with bisphosphonate-related osteonecrosis of the jaw (see Tables 7 and 8).22, The investigators did a per-protocol analysis (actual treatment received) because of the relatively large amount of crossover. Participants were evaluated at 3, 6, 12, and 18 months. At 3 months, significantly more patients receiving HBOT as an adjunct to standard care experienced improvements in lesion size and number compared with patients receiving only standard care. When the change from baseline to 6, 12, or 18 months was examined, there were no statistically significant differences between groups in the proportion of patients with improvement or in the proportion of those who healed completely at any time point. This trial had a number of methodologic limitations (eg, unblinded, crossover, per-protocol analysis rather than intention-to-treat). A disadvantage of the per-protocol analysis is that randomization is not preserved, and the 2 groups may differ on characteristics that affect outcomes. Table 7. Characteristics of Trials Assessing HBOT for Bisphosphonate-Related Osteonecrosis of the Jaw

Treatment Study (Year)

Countries Sites Dates Participants Active (n=25)

Comparator (n=21)

Freiberger et al (2012)22,

United States

NRa 2006-2010

Patients with bisphosphonate-related osteonecrosis of the jaw

· Hyperbaric oxygen plus standard oral care · 100% oxygen at 2 ATA · 40 treatments

Standard oral care (antiseptic rinses, surgery, and antibiotics)

ATA: atmospheres absolute; HBOT: hyperbaric oxygen therapy; NR: not reported; RCT: randomized controlled trial. a Number of sites not reported, though all oncologists, dentists, and oral-maxillofacial surgeons in the referral area of central North Carolina, southern Virginia, and northern South Carolina were eligible to participate.






Table 8. Results of Trials Assessing HBOT for Bisphosphonate-Related Osteonecrosis of the Jaw Improved, % (n) Healed, % (n)

Study (Year) 3 Months

Between-Group P Value

18 Months


3 Months


18 Months


Freiberger et al (2012)22,

46 46 46 46

HBOT 68.0 (25)

0.03 58.3 (12)

0.31 36.0 (25)

0.04 33.3 (12)

1.0

Control 35.0 (20)

33.3 (6) 10.0 (20)

33.3 (6)

HBOT: hyperbaric oxygen. Section Summary: Bisphosphonate-Related Osteonecrosis of the Jaw One RCT evaluated HBOT for patients with bisphosphonate-related osteonecrosis of the jaw. This unblinded study reported initial benefits at the 3-month follow-up; however, there were no significant benefits of HBOT for most health outcomes compared with standard care in the long-term (6 months to 2 years). Additional evidence from RCTs is needed to permit conclusions on the impact of HBOT on health outcomes in patients with bisphosphonate-related osteonecrosis of the jaw. Systemic Hyperbaric Oxygen Therapy for Necrotizing Soft Tissue Infections Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with necrotizing soft tissue infections. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for necrotizing soft tissue infections improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with necrotizing soft tissue infections. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication and surgical therapy. Medications prescribed for necrotizing soft tissue infection may include antibiotics. Surgical therapy can include debridement. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival, symptoms, and change in disease status. Timing The existing literature evaluating systemic HBOT as a treatment for necrotizing soft tissue infections has varying lengths of follow-up. However, given the severity of the infection, at least one year of follow-up is considered necessary to demonstrate efficacy.





Setting Patients with necrotizing soft tissue infections are managed by surgeons, wound care specialists, and infectious disease specialists in an inpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. A Cochrane review by Levett et al (2015) evaluated the literature on HBOT as adjunctive therapy for necrotizing fasciitis.23, No RCTs were identified. Previously, a systematic review by Jallali et al (2005) identified only a few retrospective studies with small sample sizes.24, Findings from these studies were inconsistent. A retrospective cohort study (2009) compared outcomes in 48 patients at 1 center who received adjunctive HBOT for necrotizing soft tissue infections with those in 30 patients at a different center who did not receive HBOT.25, There were no significant differences in the mortality rates between the HBOT group (8% [4/48]) and the non-HBOT group (13% [4/30]; p=0.48). The median number of days in the intensive care unit and the median number of days in the hospital also did not differ significantly between groups. There was a higher median number of débridement procedures per person in the HBOT group (3.0) than in the non-HBOT group (2.0; p=0.03). Section Summary: Necrotizing Soft Tissue Infections No RCTs have evaluated HBOT for necrotizing soft tissue infection. A retrospective cohort study did not find a difference in outcomes after HBOT or standard care. Systemic Hyperbaric Oxygen Therapy for Acute Coronary Syndrome Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with acute coronary syndrome. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for acute coronary syndrome improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with acute coronary syndrome. Interventions The therapy being considered is systemic HBOT.







Comparators Comparators of interest include medication and surgical therapy. Medication prescribed for the treatment of acute coronary syndrome may include thrombolytics, nitroglycerin, antiplatelet drugs, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocks and statins. Surgical therapy can include angioplasty and stenting and coronary bypass surgery. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival, symptoms, change in disease status, and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for acute coronary syndrome has varying lengths of follow-up. However, longer term follow-up does provide better opportunity for analyses of outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with acute coronary syndrome are managed by emergency physicians, cardiologists, and intensivists in an inpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. A 2015 Cochrane review by Bennett et al identified 6 trials (total N=665 patients) evaluating HBOT for acute coronary syndrome (see Table 9).26, Included studies were published between 1973 and 2007. All studies included patients with acute myocardial infarction; a study also included individuals with unstable angina. Additionally, all trials used HBOT, administered between 2 and 3 ATA, for 30 to 120 minute sessions, as an adjunct to standard care. Control interventions varied; only a trial described using a sham therapy to blind participants to treatment group allocation. In a pooled analysis of data from 5 trials, there was a significantly lower rate of death in patients who received HBOT compared with a control intervention. Due to the variability of outcome reporting across studies, few other pooled analyses could be conducted. Three trials reported outcomes related to left ventricular function. One did not find a statistically significant improvement in contraction with HBOT, while 2 trials showed left ventricular ejection fraction improved significantly with HBOT. Reviewers noted that, although some evidence from small trials correlated HBOT with a lower risk of death, larger trials with high-quality methods were needed to determine which patients, if any, could be expected to derive benefit from HBOT.





Table 9. Systematic Reviews of Trials Assessing HBOT for Acute Coronary Syndrome Study (Year)

Literature Search



Jun 2010

6 Adults with acute coronary syndrome, with or without S-T segment elevation

665 RCTs · Pooled analyses of 5 trials (n=614) reported a lower mortality rate for patients in the HBOT group vs the control (RR=0.58; 95% CI, 0.36 to 0.92) · Left ventricular outcomes, 3 trials total: 1 trial reported no difference in contraction (RR=0.09; 95% CI, 0.01 to 1.4) and pooled analyses of 2 trials (n=190) found significant improvements in LVEF with HBOT (MD=5.5%; 95% CI, 2.2% to 8.8%)

CI: confidence interval; HBOT: hyperbaric oxygen therapy; LVEF: left ventricular ejection fracture; MD: mean difference; RCT: randomized controlled trial; RR: relative risk. Section Summary: Acute Coronary Syndrome A Cochrane review of 6 RCTs found insufficient evidence that HBOT is safe and effective for acute coronary syndrome. One pooled analysis of data from 5 RCTs found a significantly lower rate of death with HBOT than with a comparison intervention; however, larger, higher quality trials are needed. Three trials measuring left ventricular function report inconsistent results. Systemic Hyperbaric Oxygen Therapy for Acute Ischemic Stroke Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with acute ischemic stroke. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for acute ischemic stroke improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with acute ischemic stroke. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include administration of tissue plasminogen activator and endovascular procedures. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival, symptoms, change in disease status, and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for acute ischemic stroke has varying lengths of follow-up, ranging from none to 6 months. In the systematic review described





below, all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, six months to one year or more of follow-up is considered necessary to demonstrate efficacy. Setting Patients with acute ischemic stroke are managed by emergency physicians, cardiologists, and intensivists in an inpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. In a 2014 Cochrane systematic review of RCTs, Bennett et al evaluated HBOT for acute ischemic stroke (see Table 10).27, Reviewers identified 11 RCTs (total N=705 participants) that compared HBOT with sham HBOT or no treatment. Reviewers could pool study findings for only 1 outcome (mortality at 3-6 months), and no difference was detected between the treatment groups for that outcome. There was heterogeneity in the participants enrolled and in the clinical and functional outcomes measured across the studies. Table 10. Systematic Reviews of Trials Assessing HBOT for Acute Ischemic Stroke

Study (Year)

Literature Search



Apr 2014

11 Patients with acute ischemic stroke, defined as sudden neurologic deficit of vascular origin for which hemorrhage was excluded by CT or MRI

705 RCTs Pooled analyses of 4 trials (n=144) found no difference in mortality at 3 to 6 mo (RR=0.97; 95% CI, 0.34 to 2.75)

CI: confidence interval; CT: computed tomography; HBOT: hyperbaric oxygen therapy; MRI: magnetic resonance imaging; RCT: randomized controlled trial; RR: relative risk. Section Summary: Acute Ischemic Stroke A Cochrane review of RCTs conducted a pooled analysis of 4 RCTs, and found no significant difference in mortality rates at 3 to 6 months when patients with acute ischemic stroke were treated with HBOT or a sham intervention. Additional RCT data are needed to permit conclusions on the impact of HBOT on the health outcome in patients with acute ischemic stroke. Systemic Hyperbaric Oxygen Therapy for Motor Dysfunction Associated with Stroke Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with motor dysfunction associated with stroke. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for motor dysfunction associated with stroke improve net health outcomes?






The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with motor dysfunction associated with stroke. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include physical therapy. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for motor dysfunction associated with stroke had a treatment-group follow-up time of two months. In the RCT described below, longer follow-up was recommended to fully observe outcomes. Therefore, three months to one year or more of follow-up is considered necessary to demonstrate efficacy. Setting Patients with motor dysfunction associated with stroke are actively managed by physical therapists, physiatrists, and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. Efrati (2013) et al published an RCT evaluating HBOT for treatment of neurologic deficiencies associated with a history of stroke (see Tables 11 and 12).28, Patients in the treatment group were evaluated at baseline and 2 months. For patients in the delayed treatment control group, outcomes were evaluated at 4 months after crossing over and receiving HBOT. Outcome measures included the National Institutes of Health Stroke Scale, which was measured by physicians blinded to treatment group, and several patient-reported quality of life (QOL) and functional status measures. At the 2-month follow-up, there was a statistically significant improvement in function in the HBOT group compared with the control group, as measured by the National Institutes of Health Stroke Scale, QOL scales, and the ability to perform activities of daily living. These differences in outcome measures were accompanied by improvements in single-photon emission computed tomography imaging in the regions affected by stroke. For the delayed treatment control group, there was a statistically significant improvement in function





after HBOT compared with before HBOT. This RCT raises the possibility that HBOT may induce improvements in function and QOL for poststroke patients with motor deficits. However, the results are not definitive, as the RCT was small and enrolled a heterogeneous group of poststroke patients. The trial was not double-blind and most outcome measures, except for National Institutes of Health Stroke Scale, were patient-reported and prone to the placebo effect. Also, there was a high total dropout rate (20%) at the 2-month follow-up. Larger, double-blind studies with longer follow-up are needed to corroborate these results. Table 11. Characteristics of Trials Assessing HBOT for Motor Dysfunction Associated with Stroke



Comparator (n=29)

Efrati et al (2013)28,

Israel 1 2008-2010

Patients ≥18 y with ischemic or hemorrhagic stroke 6 to 36 mo prior to inclusion with ≥1 motor dysfunction

· Hyperbaric oxygen · 100% oxygen at 2 ATA · 40 times over 2 mo

Same as active, delayed after 2 mo

ATA: atmospheres absolute; HBOT: hyperbaric oxygen therapy. Table 12. Results of Trials Assessing HBOT for Motor Dysfunction Associated with Stroke

National Institutes of Health Stroke Scale

Activities of Daily Livinga

Study (Year) Baseline 2 Months Between- Group P Value

Baseline 2 Months Between- Group P Value


50 50 50 50

Mean HBOT (SD) 8.5 (3.6) 5.5 (3.6) 0.004 16.1 (6.5) 12.8 (7.3) 0.02 Mean control (SD) 8.7 (4.1) 8.3 (4.3) 17.4 (9.5) 17.5 (9.5)

HBOT: hyperbaric oxygen; SD: standard deviation. a Activities of Daily Living: 16 functions scored across a range whether patient was independent to did not perform at all. Range: 0 (best) to 51 (worst). Section Summary: Motor Dysfunction Associated with Stroke One crossover RCT evaluated HBOT in patients with a recent history of stroke. The RCT reported better outcomes at 2 months with HBOT than with delayed treatment. However, the trial had a number of methodologic limitations, making it difficult to draw conclusions about the efficacy of HBOT for this indication. Double-blind RCTs that address potential bias in subjective outcomes and studies with adequate follow-up are needed. Systemic Hyperbaric Oxygen Therapy for Bell Palsy Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with Bell palsy. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for Bell palsy improve net health outcomes? The following PICOTS were used to select literature to inform this review.






Patients The relevant population of interest is individuals with Bell palsy. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include self-care (eg, artificial tears, eyepatch) and medication. Medications prescribed for Bell palsy may include steroids and antiviral drugs. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms, change in disease status, and functional outcomes. Timing There is a lack of published information analyzing the efficacy of systemic HBOT in individuals with Bell palsy. However, in order to analyze long term outcomes of function, symptoms, and change in disease status, follow-up ranging from 3 months or one year or more is considered necessary to demonstrate efficacy. Setting Patients with Bell palsy are actively managed by neurologists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. Holland (2012) et al published a Cochrane review evaluating HBOT in adults with moderate-to-severe Bell palsy.29, The literature search, conducted through January 2012, identified 1 RCT with 79 participants, but this trial did not meet reviewers’ prespecified selection standards because the outcome assessor was not blinded to treatment allocation. The trial was therefore excluded with no further analysis. Section Summary: Bell Palsy There is a lack of evidence on use of HBOT for Bell palsy. A Cochrane review did not identify any eligible RCTs; the single RCT identified lacked blinded outcome assessment. Well-conducted RCTs are needed.





Systemic Hyperbaric Oxygen Therapy for Traumatic Brain Injury Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with traumatic brain injury. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for traumatic brain injury improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with traumatic brain injury. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication, surgical therapy, and rehabilitation protocols. Medications prescribed for traumatic brain injury may include diuretics, anti-seizure drugs, and coma-inducing drugs. Emergency surgery is used to minimize damage to brain tissues and can follow on the removal of hematomas, repairing skull fractures, stopping bleeding in the brain, and opening a window in the skull. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival, symptoms, change in disease status, and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for traumatic brain injury has varying lengths of follow-up. In the systematic reviews described below, all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with traumatic brain injury are actively managed by neurosurgeons in an inpatient clinical setting. After immediate emergency care, neurologists, physiatrists, physical therapists and primary care providers manage patients in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:







Studies with duplicative or overlapping populations were excluded. A 2016 meta-analysis by Wang et al assessed HBOT for treatment of traumatic brain injury (TBI see Table 14).30, Eight studies (total N=519 participants) met the eligibility criteria. HBOT protocols varied across studies in the levels of oxygen and the length and frequency of treatments. The primary outcome was change in the Glasgow Coma Scale score. A pooled analysis of 2 studies found a significantly greater improvement in the mean Glasgow Coma Scale score in the HBOT group compared with control groups. Mortality (a secondary outcome) was reported in 3 of the 8 studies. Pooled analysis of these 3 studies found a significantly lower overall mortality rate in the HBOT group than in the control group. Another 2016 systematic review, by Crawford et al, did not conduct pooled analyses (see Table 13).31, Reviewers identified 12 RCTs evaluating HBOT for patients with TBI. Using SIGN 50 criteria, 8 trials were rated acceptable and 4 rated low. Four trials, all rated as having acceptable quality, addressed patients with mild TBI and compared HBOT with sham. None found statistically significant differences between groups on outcomes (ie, postconcussive symptom severity, psychological outcomes). Seven trials evaluated HBOT for the acute treatment of patients with moderate-to-severe TBI. Four were rated as acceptable quality and three as low quality. Study protocols and outcomes varied and none used a sham control. Three acceptable quality studies with standard care controls reported the Glasgow Outcome Scale score and mortality rate. In two of them, outcomes were better with HBOT than with standard care; in the third study, outcomes did not differ significantly. In 2012, a Cochrane review by Bennett et al evaluated HBOT as adjunctive therapy for acute TBI (see Table 13).32, Reviewers identified 7 RCTs comparing a standard intensive treatment regimen with the same treatment regimen plus HBOT. Reviewers did not include studies with interventions in specialized acute care settings. The HBOT regimens varied among studies; eg, the total number of individual sessions varied from 3 to 40. None of the trials used sham treatment or blinded staff treating patients, and only one had blinding of outcome assessment. Allocation concealment was inadequate in all studies. The primary outcomes of the review were mortality and functional outcomes. A pooled analysis of data from 4 trials showed that adding HBOT to standard care decreased mortality, but did not improve functional outcome at final follow-up. The unfavorable functional outcome was commonly defined as a Glasgow Outcome Scale score of 1, 2, or 3, which are described as “dead,” “vegetative state,” or “severely disabled,” respectively. Studies were generally small and judged to have a substantial risk of bias. Also, several trials on mild TBI in military populations have been published; they did not find significant benefits of HBOT compared with sham treatment.33,34,35, In 2015, Miller et al evaluated HBOT in 72 military service members with symptoms continuing at least 4 months after mild TBI.35, Patients were randomized to 40 daily HBOT sessions at 1.5 atm, 40 sham sessions consisting of room air at 1.2 atm or standard care with no hyperbaric chamber sessions. The primary outcome was change in Rivermead Post-Concussion Symptoms Questionnaire score. A cutoff of 15% improvement was deemed clinically important, which translates to a change score of at least 2 points on the Rivermead Post-Concussion Symptoms Questionnaire-3 subscale. The proportion of patients who met this prespecified change on the Rivermead questionnaire was 52% in the HBOT group, 33% in the sham group, and 25% in the standard care-only group. The difference between rates in the HBOT and sham groups was not statistically significant (p=0.24). None of the secondary outcomes significantly favored the HBOT group. A criticism of this trial, as











well as the other military population studies, was that patient response in the sham group was not due to a placebo effect but to an intervention effect of slightly increased atmospheric pressure (1.2 atm).36, Other researchers have noted that room air delivered at 1.2 atm would not be considered an acceptable therapeutic dose for any indication, and especially for a condition with persistent symptoms like post-concussive syndrome. Table 13. Systematic Reviews of Trials Assessing HBOT for Traumatic Brain Injury

Study (Year)

Literature Search


Wang et al (2016)30,

Dec 2014 8 Patients with mild or severe traumatic brain injury

519 RCTs and 2-arm prospective studies

· Pooled analyses of 2 trials (n=120) found significant improvements in GCS score change (3.1; 95% CI, 2.3 to 3.9) in HBOT vs control · Pooled analyses of 3 trials (n=263) found lower risk of mortality among patients treated with HBOT vs controls (OR=0.3; 95% CI, 0.2 to 0.6)

Crawford et al (2016)31,

Aug 2014 12 Military and civilian patients with traumatic brain injury

RCTs · Pooled analyses not performed · Among 3 trials with GCS outcomes, 2 reported improvements with HBOT and 1 found no difference · 4 trials assessed as acceptable quality did not find significant differences in symptom severity or psychological outcomes


Mar 2012 7 Patients with acute traumatic brain injury following blunt trauma

571 RCTs · Pooled analyses of 4 trials (n=385) found that adding HBOT to standard care decreased mortality vs standard care alone (RR=0.7; 95% CI, 0.5 to 0.9) · Pooled analyses of 4 trials (n=380) reported no difference in functional status at final follow-up between groups (RR=1.9; 95% CI, 0.9 to 4.1

CI: confidence interval; GCS: Glasgow Coma Scale; HBOT: hyperbaric oxygen therapy; OR: odds ratio; PTSD: post-traumatic stress disorder; RCT: randomized controlled trial; RR: relative risk. Section Summary: Traumatic Brain Injury A number of RCTs and systematic reviews have been published. RCTs were heterogeneous regarding intervention protocols, patient populations, and outcomes reported. Pooled analyses were only conducted on a minority of the published RCTs, and these analyses had inconsistent findings. Additionally, there was some overlap in RCTs included in the reviews. There is a lack of consistent evidence from well-conducted trials that HBOT improves the health outcome for patients with TBI. Systemic Hyperbaric Oxygen Therapy for Inflammatory Bowel Disease Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with inflammatory bowel disease.








The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for inflammatory bowel disease improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with inflammatory bowel disease. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication and surgical therapy. Medications prescribed for inflammatory bowel disease may include anti-inflammatory drugs, immune systems suppressors, antibiotics, anti-diarrheal medications, pain relievers, iron supplements, and calcium and vitamin D supplements. Surgical therapy can include ileal pouch anal anastomosis. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms, change in disease status, and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for inflammatory bowel disease has varying lengths, though many of the studies in the systematic review reported below only followed patients during treatment or for a short time after. Nearly all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with inflammatory bowel disease are managed by gastroenterologists and primary care providers in a clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. A 2014 systematic review by Dulai et al examined the evidence on HBOT for inflammatory bowel disease (Crohn disease, ulcerative colitis; see Table 14).37, The review was not limited by study design. One RCT identified was published in 2013; it was open-label and included 18 patients with ulcerative colitis.38, Patients were randomized to standard medical therapy only (n=8) or medical therapy plus HBOT (n=10). The hyperbaric oxygen intervention consisted of 90 minutes






of treatment at 2.4 atm, 5 days a week for 6 weeks (total of 30 sessions). The primary outcome was the Mayo score, which has a potential range of 0 to 12, consisting of 4 components (bleeding, stool frequency, physician assessment, and endoscopic appearance) rated from 0 to 3, and added for a final score.39 Patients with a score of 6 or more are considered to have moderate-to-severe active disease. At follow-up, there was no significant difference between groups in the Mayo score; the median score at 6 months was 0.5 in the HBOT group and 3 in the control group (p value not reported). Also, there were no significant differences in any secondary outcomes, including laboratory tests and fecal weight. This small trial might have been underpowered. Overall, reviewers found that the selected studies had a high risk of bias, due to attrition and reporting bias. Table 14. Systematic Reviews of Studies Assessing HBOT for Inflammatory Bowel Disease

Study (Year)

Literature Search


Dulai et al (2014)37,

Dec 2013 17 Patients with ulcerative colitis or Crohn disease

· Ulcerative colitis (n=327); · Crohn disease (n=286)

· 11 case reports · 3 case series · 2 case-control · 1 RCT

· Overall HBOT response rate across studies: 86% · 1 RCT (N=18) reported no difference in outcomes among patients with ulcerative colitis treated with HBOT vs HBOT plus medical therapy

HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial. Section Summary: Inflammatory Bowel Disease Only 1 small RCT has been published, and it did not find a significant improvement in health outcomes when HBOT was added to standard medical therapy. A systematic review of RCTs and observational studies found heterogeneity in HBOT protocols and high rates of bias in the literature (eg, attrition, reporting bias). Systemic Hyperbaric Oxygen Therapy for Idiopathic Sudden Sensorineural Hearing Loss Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies for individuals with idiopathic sudden sensorineural hearing loss. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for idiopathic sudden sensorineural hearing loss improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with idiopathic sudden sensorineural hearing loss. Interventions The therapy being considered is systemic HBOT alone or as an adjunct to medical therapy.

https://www.evidencepositioningsystem.com/BCBSA/html/_w_ce3a030c593696e527c5de33ad90941b76e892e28c1fa7ee/#_ENREF_39





Comparators Comparators of interest include medical therapy. Medications prescribed for idiopathic sudden sensorineural hearing loss may include systemic and intratympanic steroids, antiviral and hemodilution agents and, mineral, vitamin, and herbal supplements. Outcomes The general outcomes of interest are symptoms, change in disease status, and functional outcomes. Timing Follow-up for the evaluation of systemic HBOT as a treatment for idiopathic sudden sensorineural hearing loss would be weeks to months after early intervention. Longer follow-up of at least one year is necessary to demonstrate efficacy. Setting Patients with idiopathic sudden sensorineural hearing loss are managed by otolaryngologists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. Systematic Reviews A 2012 Cochrane review by Bennett et al on HBOT for idiopathic sudden sensorineural hearing loss (ISSNHL) and/or tinnitus identified 7 RCTs (N=392; see Table 15).40, Treatment of tinnitus is covered in evidence review 8.01.39. Studies were small and generally of poor quality. Randomization procedures were only described in 1 study, and only 1 study stated they blinded participants to treatment group assignment using sham therapy. Six studies included time-based entry criteria for hearing loss and/ortinnitus (48 hours in 3 studies, 2 weeks in 2 studies, 6 months in 1 study). The dose of oxygen per treatment session and the treatment protocols varied across studies (eg, the total number of treatment sessions ranged from 10-25). All trials reported on the change in hearing following treatment, but specific outcomes varied. Two trials reported the proportion of participants with more than 50% and more than 25% return of hearing at the end of therapy. A pooled analysis of these studies did not find a statistically significant difference in outcomes between the HBOT and the control groups at the level of 50% or higher but did find a significantly higher rate of improvement at the level of 25% or higher (see Table 15). A pooled analysis of 4 trials found a significantly greater mean improvement in hearing over all frequencies with HBOT compared with control. Reviewers stated that, due to methodologic shortcomings of the trials and the modest number of patients, results





of the meta-analysis should be interpreted cautiously; they did not recommend the use of HBOT for treating ISSNHL. Rhee et al (2018) performed a systematic review and meta-analysis through February 2018 for patients comparing HBOT plus medical therapy (MT) with medical therapy alone for SSNHL treatment.41,Randomized clinical trials and nonrandomized studies were included. The main outcomes considered were complete hearing recovery, any hearing recovery, and absolute hearing gain. Nineteen studies (3 randomized and 16 nonrandomized) with a total of 2401 patients (mean age, 45.4 years; 55.3% female) were included. In the HBOT+MT group, rates of complete hearing recovery and any hearing recovery were 264/897 (29.4%) and 621/919 (67.6%), respectively, and in the MT alone group were 241/1167 (20.7%) and 585/1194 (49.0%), respectively. Pooled HBOT+MT also showed favorable pooled results from random-effects models for both complete hearing recovery (OR, 1.61; 95% CI, 1.05-2.44) and any hearing recovery (OR, 1.43; 95% CI, 1.20-1.67). The study was limited by the following: (1) differences in clinical and methodological characteristics of selected studies, (2) considerable heterogeneity, (3) the possibility of measure or unmeasured confounder effects, and (4) difficulty in evaluating the benefit of treatment due to a substantial proportion of patients experiencing spontaneous recovery. Table 15. Systematic Reviews and Meta-Analyses of Trials Assessing HBOT for Idiopathic Sudden Sensorineural Hearing Loss

Study (Year) Literature Search


Bennett (2012)40, May 2012

7 Patients with idiopathic SSNHL and/or tinnitus

392 RCTs · Pooled analyses of 2 RCTs (n=114) showed HBOT did not result in >50% improvement in pure tone average threshold (RR=1.5; 95% CI, 0.9 to 2.8), but was able to achieve >25% improvement (RR=1.4; 95% CI, 1.1 to 1.8) · Pooled analyses of 4 trials (n=169) found a significantly greater mean improvement in hearing over all frequencies with HBOT vs control (mean difference, 15.6 dB; 95% CI, 1.5 to 29.8 dB)

Rhee (2018)41, Feb 2018 19 Patients with with SSNHL

2401 3 RCTs, 16 nonRCTs

· Pooled results significantly favored the HBOT and MT group over MT alone group for complete hearing recovery (pooled OR: 1.61; CI: 1.05-2.44) and for hearing recovery (pooled OR: 1.43, CI: 1.20-1.67)

CI: confidence interval; HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial; RR: relative risk; SSNHL: sudden senosorineural hearing loss. Randomized Controlled Trials Cvorovic et al (2013) conducted an RCT that included 50 patients with ISSNHL who had failed primary therapy with intravenous steroids.42, This study was included in the 2018 systematic review. Patients were randomized to HBOT (20 sessions, 5 daily sessions per week) or intratympanic steroid injection (4 injections in 13 days). The HBOT sessions consisted of 10 minutes of compression on air, 60 minutes of 100% oxygen at 2 atm, and 10 minutes of








decompression on air. Outcomes were change in the mean hearing thresholds at each of 5 frequencies (0.25, 0.5, 1, 2, and 4 kHz). After treatment, there were no statistically significant differences in mean hearing thresholds at 4 of the 5 frequencies. The exception was 2 kHz, and at that frequency, the improvement was significantly greater in the HBOT group. Nonrandomized Observational Studies: Sun et al (2018) compared the efficacy of intratympanic dexamethasone therapy and hyperbaric oxygen therapy for salvage treatment of 104 patients with refractory high-frequency SSNHL.43, Patient charts were retrospectively allocated into three groups: ITD alone group (n=31), HBO alone group (n=32), and a control group in which patients received no salvage therapy (n=41). No significant difference was found between the groups for total effective rate of hearing recovery (p=0.213); also, no significant differences were found between ITD and HBO (p=0.368) or between ITD and the control group (p=0.197). At 2 and 4 KHz, no significant differences were found between any groups; however, at 8 KHz, there was a significant difference for ITD vs HBO (p=0.049) and for ITD vs control (p=0.025), but not for HBO vs control (p=0.873). Almosnino et al (2018) conducted a matched control retrospective case series evaluating hyperbaric oxygen (HBO2) as salvage therapy for sudden sensorineural hearing loss (SSNHL).44, In total, 36 (18 received IT steroids and HBO2 and 18 received IT steroids alone) SSNHL patients >18 years were included in the study. The post-treatment pure tone average (PTA) did not vary significantly between the HBO2 (60.3 dB) and non-HBO2 (53.2 dB) groups; the mean post-treatment word recognition scores (WRSs) also did not differ significantly (HBO2 42%, WRS 51%). In the HBO2 group, 33% of patients improved from nonserviceable hearing (WRS of <50%) to serviceable hearing (WRS of ≥50%) after treatment, while 42% of non-HBO2 patients went from nonserviceable hearing to serviceable hearing (p>0.05). The study was limited by its retrospective nature, small sample size, lack of randomization, and differences in dosing and duration of treatment between patients. In a retrospective chart review of 178 idiopathic SSNHL patients, Xie et al (2018) evaluated potential prognostic factors of idiopathic SSNHL treated with HBOT.45, Overall recovery rate was 37.1%; complete recovery was 19.7% and partial recovery was 17.4%. Higher initial hearing threshold and later onset of HBOT were associated with a poor prognosis in idiopathic SSNHL patients treated with HBOT. The study was limited by its retrospective chart review design. Section Summary: Idiopathic Sudden Sensorineural Hearing Loss A Cochrane review of RCTs had mixed findings from studies that included individuals with tinnitus. Some outcomes (ie, improvement in hearing of all frequencies, >25% return of hearing) were better with HBOT than with a control intervention, but more than 50% return of hearing did not differ significantly between groups. There was important variability in the patients enrolled in the studies. A subsequent systematic review had similarly limited conclusions due to the inclusion of non-randomized studies. One RCT included in this review included patients with ISSNHL and found no differences in HBOT treatment compared with steroid injections in mean hearing thresholds at 0.25, 0.5, 1, and 4 kHz; however, a significant difference was detected at the 2-kHz level. Nonrandomized studies of HBOT used as adjunctive therapy did not support incremental value.







Systemic Hyperbaric Oxygen Therapy for Delayed-Onset Muscle Soreness Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with delayed-onset muscle soreness. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for delayed-onset muscle soreness improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with delayed-onset muscle soreness. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include conservative care (eg, massage) and medication (eg, pain relief). Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for delayed-onset muscle soreness has varying lengths of follow-up. In the systematic review described below, all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one month of follow-up is considered necessary to demonstrate efficacy. Setting Patients with delayed-onset muscle soreness are managed by physical therapists, physiatrists, and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. In a 2005 Cochrane review updated in 2010, Bennett et al identified 9 small RCTs on HBOT for delayed-onset muscle soreness and closed soft tissue injury (see Table 16).46, Included trials were published between 1996 and 2003. Methodologic quality was assessed as fair to high.





Pooled analysis showed significantly higher pain in the group receiving HBOT compared with control. There were no between-group differences in long-term pain outcomes or other measures (eg, swelling, muscle strength). Table 16. Systematic Reviews of Trials Assessing HBOT for DOMS

Study (Year)

Literature Search



Feb 2010 9 Patients with acute closed soft tissue injuries or DOMS

219 RCTs · 2 trials on closed soft tissue injuries: no significant difference in time to recovery, functional outcomes, or pain · 7 DOMS trials, pooled: significantly higher pain at 48 and 72 h in HBOT group, 0.9 (95% CI, 0.09 to 1.7); no differences in long-term pain, swelling, or muscle strength

CI: confidence interval; DOMS: delayed-onset muscle soreness; HBOT: hyperbaric oxygen therapy. Section Summary: Delayed-Onset Muscle Soreness A Cochrane review of RCTs with fair to high methodologic quality found worse short-term pain outcomes with HBOT than with a control condition and no difference in longer term pain or other outcomes (eg, swelling). Systemic Hyperbaric Oxygen Therapy for Autism Spectrum Disorder Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with autism spectrum disorder. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for autism spectrum disorder improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with autism spectrum disorder. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include behavioral therapy and medication. Behavioral therapy may include anger management, family therapy, applied behavior analysis, etc. Medications prescribed may include antipsychotics. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for autism spectrum disorder had a follow-up of ten weeks. However, longer term follow-up may show difference between the





intervention and comparators. Therefore, at least six months of follow-up is considered necessary to demonstrate efficacy. Setting Patients with autism spectrum disorder are actively managed by behavioral therapists and psychologists in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. A 2016 Cochrane review by Xiong et al identified 1 RCT evaluating systemic HBOT for people with autism spectrum disorder that met eligibility criteria (see Table 17).47, Criteria included a hyperbaric oxygen intervention using 100% oxygen at more than 1 atm. The trial, published by Sampanthaviat et al (2012), was considered low-quality evidence as assessed by the GRADE approach. The trial randomized children with autism to receive 20 one-hour sessions with HBOT or sham air (n=30 per group).48,The primary outcome measures were change in Autism Treatment Evaluation Checklist and Clinical Global Impression scores, evaluated separately by clinicians and parents. There were no statistically significant differences between groups for either primary outcome. Posttreatment clinician-assessed mean scores on Autism Treatment Evaluation Checklist were 52.4 in the HBOT group and 52.9 in the sham air group. Table 17. Systematic Reviews of Trials Assessing HBOT for Autism Spectrum Disorder

Study (Year)

Literature Search

Studies Participants N Design Results Mean Difference

Xiong et al (2016)47,

Dec 2015 1 Children aged 3-9 y with autism spectrum disorder

60 RCT · Parental assessed ATEC: 1.2 (95% CI, -2.2 to 4.6) · Clinician assessed ATEC: 1.5 (95% CI, -1.3 to 4.5)

ATEC: Autism Treatment Evaluation Checklist; CI: confidence interval; HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial. Section Summary: Autism Spectrum Disorder A Cochrane review identified a single small low-quality RCT on HBOT for autism spectrum disorder and that trial did not find significantly improved outcomes with HBOT vs sham. Systemic Hyperbaric Oxygen Therapy for Cerebral Palsy Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with cerebral palsy. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for cerebral palsy improve net health outcomes?







The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with cerebral palsy. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include physical therapy and medication. Medications directed at isolated (eg, onabotulinumtoxinA) and generalized spasticity (eg, diazepam, dantrolene, and baclofen) may be prescribed for cerebral palsy. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for cerebral palsy has varying lengths of follow-up. In the trials described below, all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with cerebral palsy are managed by physical therapists, physiatrists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. Two published RCTs were identified on use of HBOT for cerebral palsy (see Tables 18 and 19). In 2012, Lacey et al published a double-blind RCT that included 49 children ages 3 to 8 years with spastic cerebral palsy.49, Participants were randomized to 40 treatments with HBOT or hyperbaric air to simulate 21% oxygen at room air. The primary efficacy outcome was change in the Gross Motor Function Measure global score. The trial was stopped early due to futility when an interim analysis indicated that there was less than a 2% likelihood that a statistically significant difference between groups would be found.





Collet et al (2001) randomized 111 children with cerebral palsy to 40 treatments over a 2-month period of HBOT or slightly pressurized room air.50, Investigators found similar improvements in outcomes such as gross motor function and activities of daily living in both treatment groups. In 2017, an observational study by Long et al evaluated the effects of HBOT as a treatment for sleep disorders in children with cerebral palsy (N=71).51, Children, aged 2 to 6 years, underwent 60-minute sessions of 100% oxygen, at 1.6 ATA, for 15 to 20 sessions total. Results showed improvements in average time to fall asleep, average hours of sleep duration, and an average number of night awakenings after 10 HBOT sessions compared with pretreatment. Table 18. Characteristics of Trials Assessing HBOT for Cerebral Palsy


Countries Sites Dates Participants Active Comparator

Lacey et al (2012)49,

United States

2 2005- 2009

Children aged 3-8 y with spastic CP

· n=25 · Hyperbaric oxygen · 100% oxygen at 1.5 ATA · 40 times over 2 mo

· n=24 · Hyperbaric air · 14% oxygen at 1.5 ATA · 40 times over 2 mo

Collet et al (2001)50,

Canada 17 NR Children aged 3-2 y with CP

· n=57 · Hyperbaric oxygen · 100% oxygen at 1.75 ATA · 40 times over 2 mo

· n=54 · Slightly pressurized air · 100% oxygen at 1.3 ATA · 40 times over 2 mo

ATA: atmospheres absolute; CP” cerebral palsy; HBOT: hyperbaric oxygen therapy; NR: not reported. Table 19. Results of Trials Assessing HBOT for Cerebral Palsy

Study (Year) Mean Change GMFMa (95% CI)

Between-Group Difference

(95% CI)

Mean Change, Functional Skill

Between-Group Difference (95% CI)

Lacey et al (2012)49,

46 46

HBOT 1.5 (-0.3 to 3.3) 0.9 (-1.5 to 3.3) 4.4 (2.3 to 6.5) 1.1 (-1.5 to 3.7) HBAT 0.6 (-1.0 to 2.2) 3.3 (1.6 to 5.0) Collet et al (2001)50,

Mean Change, PEDI Self Care

HBOT 2.9 (1.9 to 3.9) -0.4 (-1.7 to 0.9) 2.8 (1.6 to 4.0) 0.1 (-1.8 to 2.0) Slight pressure 3.0 (2.1 to 3.9) 2.7 (1.3 to 4.0)

CI: confidence interval; GMFM: Gross Motor Function Measure; HBOT: hyperbaric oxygen; PEDI: Pediatric Evaluation of Disability Inventory. a Positive score represents improvement in function from baseline. Section Summary: Cerebral Palsy Two RCTs and an observational study were identified. One RCT was stopped early due to futility and the other did not find significantly better outcomes with HBOT than with a sham intervention. The observational study, which focused on improving sleep in patients with cerebral palsy, reported improvements following HBOT. Systemic Hyperbaric Oxygen Therapy for Vascular Dementia










Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with vascular dementia. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for chronic diabetic ulcers improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with vascular dementia. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest rehabilitation and medication (eg, cognition-enhancing medication). Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for vascular dementia reported follow-up at 12 weeks. However, longer follow-up is necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with vascular dementia are managed by neurologists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. A 2012 Cochrane review identified a small RCT evaluating HBOT for vascular dementia (see Table 20).52, This 2009 RCT, conducted in China, compared HBOT (30-day cycles of 1 hour/day for 24 days and 6 days of rest) plus donepezil to donepezil-only in 64 patients. The HBOT plus donepezil group had significantly improved cognitive function after 12 weeks of treatment, though the confidence intervals were wide due to the small sample size. Reviewers judged the trial to be of





poor quality because it was not blinded and the methods of randomization and allocation concealment were not discussed. Table 20. Systematic Reviews of Trials Assessing HBOT for Vascular Dementia

Study (Year)

Literature Search


Xiao et al (2012)52,

Dec 2011 1 Patients with vascular dementia, according to DSM- IV criteria

64 RCT · WMD of MMSE score: 3.5 (95% CI, 0.9 to 6.1) · WMD of HDS score: 3.1 (95% CI, 1.2 to 5.0)

CI: confidence interval; DSM-IV: Diagnostic and Statistical Manual for Mental Disorders Fourth Edition; HBOT: hyperbaric oxygen therapy; HDS: Hasegawa’s Dementia Rating Scale; MMSE: Mini-Mental State Examination; WMD: weighted mean difference. Section Summary: Vascular Dementia A Cochrane review identified an RCT judged to be of poor quality. This trial provided insufficient evidence to permit conclusions on the impact of HBOT on health outcomes in patients with vascular dementia. Systemic Hyperbaric Oxygen Therapy for Radiotherapy Adverse Events Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with radiotherapy adverse events. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for radiotherapy adverse effects improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with radiotherapy adverse events. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication. Medications to treat cardiovascular and pulmonary adverse events (eg, pentoxifylline), gastrointestinal toxicity (eg, amifostine, antidiarrheals), radiation-induced emesis (5-HT3), radiation cystitis (eg, phenazopyridine, oxybutynin, and flavoxate), and sexual dysfunction (eg, sildenafil and tadalafil) may be prescribed. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for radiotherapy adverse events has varying lengths of follow-up. In the systematic reviews and RCTs described below, nearly all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy.





Setting Patients with radiotherapy adverse events are actively managed by oncologists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. This indication covers adverse events of radiotherapy other than osteoradionecrosis and treatment of irradiated jaw, which was covered in an earlier indication. Spiegelberg (2010) et al conducted a systematic review of studies on HBOT to prevent or treat radiotherapy-induced head and neck injuries associated with the treatment of malignant tumors (see Table 21).53, Reviewers identified 20 studies. Protocols and conclusions varied across the studies. Eight studies included control groups; their sample sizes ranged from 19 to 78 subjects. Four studies with a control group concluded that HBOT was effective; the other four did not. Reviewers noted a paucity of RCTs, though they did not state how many RCTs were included in the review, because studies were only identified only as prospective or retrospective. Ravi (2017) et al conducted a systematic review assessing the effect of HBOT on patients with head and neck cancer who had received radiotherapy (see Table 21).13, Pooled analyses were not performed; however, summary results were discussed for the following outcomes: salivary gland function, osteonecrosis prevention, dental implant survival, and QOL. Osteonecrosis prevention and dental implant survival outcomes were discussed previously (see the Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw section). Table 21. Systematic Reviews of Studies Assessing HBOT for Radiotherapy Adverse Events

Study (Year)

Literature Search


Spiegelberg et al (2010)53,

Jun 2009

20 Patients who have received RT for malignant tumors in the head and neck

695 Prospective and retrospective studies

· Due to the heterogeneity among studies, pooled analysis was not possible · 8 studies had control groups and 4 concluded that HBOT was effective and 4concluded that HBOT was not

Ravi et al (2017)13,

Dec 2016 10 Patients who have received RT for head and neck cancer

375 Prospective case series and prospective comparative studies

· Salivary gland function: 2 case series (n=96) reported that patients receiving HBOT experienced improvements in salivary flow rates · Quality of life: 3 case series (n=106) administered








Study (Year)

Literature Search


various QOL instruments (eg, SF-36, EORTC, HADS), reporting that many subsets of the questionnaires (eg, swallowing, pain, salivary quantity) showed significant improvements with HBOT

EORTC: European Organization for Research and Treatment of Cancer; HADS: Hospital Anxiety and Depression Scale; HBOT: hyperbaric oxygen therapy; QOL: quality of life; RT: radiotherapy; SF-36: 36-Item Short-Form Health Survey. Several RCTs were identified in literature searches. A 2009 trial by Teguh et al, included in the reviews, evaluated 17 patients with oropharyngeal or nasopharyngeal cancer who were treated with radiotherapy; the trial was conducted in The Netherlands.54,HBOT was used to prevent adverse events following radiotherapy. Eight patients were randomized to 30 sessions of HBOT, administered within 2 days of completing radiotherapy, and 9 patients to no additional treatment. QOL outcomes were assessed, and the primary outcome was xerostomia at 1 year. QOL measures did not differ significantly between groups in the acute phase (first 3 months). One month after treatment, the mean visual analog scale score (0-to-10 scale) for xerostomia was 5 in the HBOT group and 6 in the control group. However, at 1 year, there was a statistically significant difference between groups in mean QOL score (0-to-100 scale) for swallowing, (7 in the HBOT group and 40 in the control group, (p<0.001). The trial is limited by its small sample size and wide fluctuations over the follow-up in QOL ratings. In a trial not included in the reviews, Gothard et al (2010) in the U.K. published findings of an RCT using HBOT for arm lymphedema occurring after radiotherapy for cancer.55, Fifty-eight patients with arm lymphedema (at least 15% increase in arm volume) following cancer treatment were randomized in a 2:1 ratio to HBOT (n=38) or usual care without HBOT (n=20). Fifty-three patients had baseline assessments, and 46 (79%) of 58 had 12-month assessments. At the 12-month follow-up, there was no statistically significant difference in the change from baseline in arm volume. Median change from baseline was -2.9% in the treatment group and -0.3% in the control group. The study protocol defined response as at least an 8% reduction in arm volume relative to the contralateral arm. By this definition, 9 (30%) of 30 of patients in the HBOT group were considered responders compared with 3 (19%) of 16 in the control group (p=NS). Other outcomes (eg, QOL scores on the 36-Item Short-Form Health Survey [SF-36]) also did not differ significantly between groups. Section Summary: Radiotherapy Adverse Events Two systematic reviews have noted a lack of RCTs evaluating HBOT for radiotherapy adverse events. One review focused on salivary gland function, osteonecrosis prevention, dental implant survival, and QOL. The available RCTs had mixed findings. One found no short-term benefit and some benefits of HBOT 12 months after radiotherapy, while the other did not find a significant benefit of HBOT 12 months after radiotherapy. An RCT not included in the reviews focused on arm lymphedema; it found no significant differences between study groups.






Systemic Hyperbaric Oxygen Therapy for Idiopathic Femoral Neck Necrosis Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with idiopathic femoral neck necrosis. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for femoral neck necrosis improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with idiopathic femoral neck necrosis. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include physical therapy, medication, and surgical therapy. Medications prescribed to treat idiopathic femoral neck necrosis may include non-steroidal anti-inflammatory drugs, osteoporosis drugs, cholesterol-lowering drugs, and blood thinners. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms, change in disease status, and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for idiopathic femoral neck necrosis analyzed HBOT therapy at six weeks of follow-up. Longer follow-up is necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with idiopathic femoral neck necrosis are actively managed by orthopedic surgeons in an inpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded.




A double-blind RCT evaluating HBOT for treatment of femoral head necrosis was published in 2010 by Camporesi et al (see Tables 22 and 23).56, The trial included 20 adults with idiopathic unilateral femoral head necrosis. Patients received HBOT or a sham treatment of hyperbaric air. Mean severity of pain on a 0-to-10 scale was significantly lower in the HBOT group than in the control group after 30 sessions (p<0.001) but not after 10 or 20 sessions. The trial did not report exact pain scores. Several range-of-motion outcomes were reported. At the end of the initial treatment period, extension, abduction, and adduction, but not flexion, was significantly greater in the HBOT group than in the control group. Longer term comparative data were not available because the control group was offered HBOT after the initial 6-week treatment period. Table 22. Characteristics of Trials Assessing HBOT for Femoral Neck Necrosis



Comparator (n=10)

Camporesi et al (2010)56,

United States

1 NR Patients with unilateral femoral neck necrosis

· Hyperbaric oxygen · 100% oxygen at 2.5 ATA · 30 sessions over 6 wk

· Hyperbaric air · 30 sessions over 6 wk

ATA: atmospheres absolute; HBOT: hyperbaric oxygen therapy; NR: not reported. Table 23. Results of Trials Assessing HBOT for Femoral Neck Necrosis

Study (Year) Median (Range) Extension,

After 10 Sessions


P Value

Median (Range) Extension,

After 30 Sessions


P Value Camporesi et al (2010)56, HBOT 7.5 (4.0-20.0) NS 20.0 (15.0-20.0) <0.001 HBAT 4.0 (3.0-6.0) 3.0 (0.0-5.0)

HBAT: hyperbaric air therapy; HBOT: hyperbaric oxygen therapy; NS: not significant. Section Summary: Idiopathic Femoral Neck Necrosis One small RCT (N=20) was identified. Six-week outcomes and results were mixed, with improvements reported in extension, abduction, and adduction, but not flexion. Significant improvements in pain were reported after 30 sessions, though no differences were detected after 10 or 20 sessions. This RCT does not provide sufficient data to permit conclusions about the efficacy of HBOT for femoral head necrosis. Systemic Hyperbaric Oxygen Therapy for Migraine Headache Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with migraine headache. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for migraine headache improve net health outcomes? The following PICOTS were used to select literature to inform this review.







Patients The relevant population of interest is individuals with migraine headache. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication. Medications prescribed to treat migraines may include antipsychotics, analgesics, non-steroidal anti-inflammatory drugs, stimulants, nerve pain relievers, Triptan, and neurotoxins. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms, change in disease status, and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for migraine has varying lengths of follow-up. In the systematic reviews described below, nearly all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one month of follow-up is considered necessary to demonstrate efficacy. Setting Patients with migraine are managed by neurologists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. A 2015 Cochrane review by Bennett et al identified 11 RCTs (total N=209 patients) comparing the effectiveness of systemic HBOT for preventing or treating migraine headache or cluster headaches with another treatment or a sham control (see Table 24).57,A pooled analysis of 3 trials focusing on migraine headaches (n=58 patients) found a statistically significant increase in the proportion of patients with substantial relief of a migraine within 45 minutes of HBOT. No other pooled analyses were conducted due to variability in outcomes reported across trials. The meta-analysis did not report data on treatment effectiveness beyond the immediate posttreatment period, and the methodologic quality of selected trials was moderate to low (eg, randomization was not well-described in any trial).





Table 24. Systematic Reviews of Trials Assessing HBOT for Migraine or Cluster Headaches Study (Year)

Literature Search



Jun 2015 11 Patients with migraine or cluster headaches

209 RCT · For 3 trials focusing on migraine headaches (n=58) of low quality, HBOT was effective in relieving migraine (RR=6.21; 95% CI, 2.4 to 16.0) · No evidence that HBOT can prevent migraine, reduce nausea or vomiting, or reduce need for rescue medication

CI: confidence interval; HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial; RR: relative risk. Section Summary: Migraine A Cochrane review identified 11 RCTs on HBOT for a migraine headache. However, only a single pooled analysis was conducted including 3 of the 11 trials. The pooled analysis found significantly greater relief of migraine symptoms with HBOT than with a comparator intervention within 45 minutes of treatment. Limitations included the availability of outcomes specific to the immediate posttreatment period, the variability of outcomes across trials, and generally low methodologic quality of trials. Systemic Hyperbaric Oxygen Therapy for Herpes Zoster Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with herpes zoster. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for herpes zoster infection improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with herpes zoster. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication. Medications prescribed to treat herpes zoster may include anti-viral drugs, anesthetics, non-steroidal anti-inflammatory drugs, analgesics, and nerve pain relievers. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for herpes zoster described below, reported outcomes of interest, but longer follow-up is necessary to fully observe





outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with herpes zoster are managed by infectious disease specialists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. Peng (2012) et al in China published an RCT evaluating HBOT for herpes zoster (see Tables 25 and 26).58, Sixty-eight patients with herpes zoster were randomized to HBOT with medication or medication treatment alone. The following outcomes were measured after 3 weeks of treatment: therapeutic efficacy, days to blister resolution, days to scar formation, and pain. Patient receiving HBOT experienced significantly improved outcomes compared with patients receiving medication alone. Limitations of the trial included a lack of blinding and long-term follow-up. Table 25. Characteristics of Trials Assessing HBOT for Herpes Zoster


Countries Sites Dates Participants Active (n=36) Comparator (n=32)

Peng et al (2012)58,

China NR 2008-2010

Patients diagnosed with herpes zoster within 2 wk

· Hyperbaric oxygen · 100% oxygen at 2.2 ATA · 2 sessions/day for 5 d · Thirty 120-min sessions; plus medications that control group received

Medication alone, including: antiviral, nerve nutritive, pain relief, and antidepressives

ATA: atmospheres absolute; HBOT: hyperbaric oxygen therapy; NR: not reported. Table 26. Results of Trials Assessing HBOT for Herpes Zoster

Study (Year) Efficacya,b Mean Days to Blister Resolutionb

Mean Days to Scar Formationb

NPRS Scoreb

Pretreatment Posttreatment Peng et al (2012)58, 68 68 68 68 68 Mean HBOT and medication (SD)

97.2% 2.8 (1.5) 11.1 (4.0) 8.0 (1.8) 1.8 (2.7)

Mean medication alone (SD)

81.3% 3.3 (1.4) 13.9 (4.3) 8.1 (1.7) 3.5 (4.1)

HBOT: hyperbaric oxygen therapy; NPRS: Numeric Pain Rating Scale. a Calculation: (number cases with healing + number cases with improvement)/(total number cases × 100).







b Between-group difference p<0.05. Section Summary: Herpes Zoster One RCT was identified. Only short-term outcomes were reported. Outcomes at the end of treatment were significantly better in the HBOT group than in the medication group. Trial limitations included lack of blinding and long-term outcomes. Systemic Hyperbaric Oxygen Therapy for Fibromyalgia Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with fibromyalgia. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for fibromyalgia improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with fibromyalgia. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication. Medications prescribed for fibromyalgia may include selective serotonin reuptake inhibitors, analgesics, non-steroidal anti-inflammatory drugs, nerve pain relievers, and muscle relaxants. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms, change in disease status, and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for fibromyalgia has varying lengths of follow-up. In the systematic reviews described below, all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with fibromyalgia are managed by neurologists, physiatrists, physical therapists, and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:







Studies with duplicative or overlapping populations were excluded. One delayed treatment RCT and a quasi-randomized trial on HBOT for fibromyalgia were identified. Efrati (2015) et al published an RCT that included 60 symptomatic women who had fibromyalgia for at least 2 years (see Tables 27 and 28).59, Patients were randomized to an immediate 2-month course of HBOT or delayed HBOT after 2 months. Forty-eight (80%) of 60 patients completed the trial. After the initial 2 months, outcomes including a number of tender points, pain threshold, and QOL (SF-36) were significantly improved in the immediate treatment group than in the delayed treatment group. After the delayed treatment group had undergone HBOT, outcomes were significantly improved compared with scores in the 2 months before HBOT treatment. These findings are not only consistent with a clinical benefit of HBOT, but also with a placebo effect. A sham control trial is needed to confirm the efficacy of HBOT in the treatment of fibromyalgia and other conditions where primary end points are pain and other subjective outcomes. Yildiz (2004) et al assessed 50 patients with fibromyalgia (see Tables 27 and 28).60, On an alternating basis, patients were assigned to HBOT or a control group. After HBOT treatment, the mean standard deviation, number of tender points, and mean visual analog scale scores were improved in patients receiving HBOT compared with controls. It is unclear whether the control group received a sham intervention that would minimize any placebo effect (ie, whether the control intervention was delivered in a hyperbaric chamber). The authors stated that the trial was double-blind, but did not provide details of patient blinding. Table 27. Characteristics of Trials Assessing HBOT for Fibromyalgia


Countries Sites Dates Participants Active Comparator


Israel 1 2010-2012

Patients with fibromyalgia based on: (1) widespread pain and (2) at least 11 of 18 tender points

· n=24 · Hyperbaric oxygen · 100% oxygen at 2 ATA · 1 session/day for 5 d · Forty 90-min sessions

· n=26 · No treatment for 2 mo, then same treatment as active group

Yildiz et al (2004)60,

Turkey NR NR Patients meeting ACR criteria for fibromyalgia, with persistent symptoms despite medical therapy and PT

· n=26 · Hyperbaric oxygen · 100% oxygen at 2.4 ATA · 1 session/day for 5 d · Fifteen 90-min sessions

· n=24 · Air · 1 ATA · 1 session/day for 5 d · Fifteen 90-minute sessions

ACR: American College of Rheumatology; ATA: atmospheres absolute; HBOT: hyperbaric oxygen therapy; NR: not reported; PT: physical therapy.








Table 28. Results of Trials Assessing HBOT for Fibromyalgia Tender Points Pain Threshold

Study (Year) Baseline After HBOT


Baseline After HBOT


Efrati et al (2015)59, 50 50 Mean HBOT (SD) 17.3 (1.4) 8.9 (6.0) <0.001 0.5 (1.2) 1.7

(0.8) <0.001

Mean control (SD) 17.7 (0.7) 17.2 (1.1)

0.7 (0.5) 0.6 (0.5)

Yildiz et al (2004)60, 50 50 Mean HBOT (SD) 15.0 (1.5) 6.0 (1.2) <0.001 0.7 (0.1) 1.3

(0.1) <0.001

Mean air (SD) 15.3 (1.2) 12.5 (1.1)

0.7 (0.1) 0.8 (0.1)

HBOT: hyperbaric oxygen therapy. Section Summary: Fibromyalgia Two RCTs assessing HBOT for fibromyalgia were identified. Both had relatively small sample sizes and methodologic limitations (eg, quasi-randomization, no or uncertain sham control for a condition with subjective outcomes susceptible to a placebo effect). Moreover, the HBOT protocols varied. Thus, the evidence is insufficient to permit conclusions on the impact of HBOT on health outcomes for patients with fibromyalgia. Systemic Hyperbaric Oxygen Therapy for Multiple Sclerosis Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with multiple sclerosis. The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for multiple sclerosis improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with multiple sclerosis. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include medication. Medications prescribed to treat multiple sclerosis include chemotherapy, anti-inflammatory drugs, immunosuppressive drugs, and steroids. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are symptoms and functional outcomes. Timing The existing literature evaluating systemic HBOT as a treatment for multiple sclerosis has varying lengths of follow-up, ranging from four weeks to six months. In the systematic review described






below, nearly all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with multiple sclerosis are managed by neurologists and primary care providers in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. Bennett (2010) et al published a systematic review on the use of HBOT for treatment of multiple sclerosis (see Table 29).61 Nine RCTs (total N=504 participants) were identified that compared the effects of HBOT with placebo or no treatment. All trials used an initial course of 20 sessions over 4 weeks, although dosages among studies varied from 1.75 ATA for 90 minutes to 2.5 ATA for 90 minutes. The primary outcome of the review was Expanded Disability Status Scale score. A pooled analysis of data from 5 trials (n=271 patients) did not find a significant difference in mean Expanded Disability Status Scale score change after 20 HBOT treatments vs control or after 6 months of follow-up. Table 29. Systematic Reviews of Trials Assessing HBOT for Multiple Sclerosis

Study (Year)

Literature Search



Jul 2009 9 Patients with multiple sclerosis, at any state or course of the condition

504 RCT EDSS score difference between groups: · At 4-wk follow-up: 0.07 (95% CI, -0.09 to 0.23) · At 6-mo follow-up: 0.22 (95% CI, -0.09 to 0.54)

CI: confidence interval; EDSS: Expanded Disability Status Scale; HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial. Section Summary: Multiple Sclerosis A Cochrane review of RCTs did not find a significant difference in outcomes when patients with multiple sclerosis were treated with HBOT vs a comparison intervention. Systemic Hyperbaric Oxygen Therapy for Individuals with Cancer who are Undergoing Radiotherapy or Chemotherapy Clinical Context and Therapy Purpose The purpose of systemic HBOT is to provide a treatment option that is an alternative or an improvement on existing therapies in patients with cancer who are undergoing radiotherapy or chemotherapy.

https://www.evidencepositioningsystem.com/BCBSA/html/_w_ce3a030c593696e527c5de33ad90941b76e892e28c1fa7ee/#_ENREF_61





The question addressed in this evidence review is: Does the use of systemic hyperbaric oxygen as a treatment for individuals with cancer who are undergoing radiotherapy or chemotherapy improve net health outcomes? The following PICOTS were used to select literature to inform this review. Patients The relevant population of interest is individuals with cancer who are undergoing radiotherapy or chemotherapy. Interventions The therapy being considered is systemic HBOT. Comparators Comparators of interest include radiotherapy or chemotherapy without HBOT. Systemic HBOT may be used as an adjunct to these comparators. Outcomes The general outcomes of interest are overall survival and change in disease status. Timing The existing literature evaluating systemic HBOT as a treatment for cancer who are undergoing radiotherapy or chemotherapy has varying lengths of follow-up, six months to five years. In the systematic review and RCT described below, nearly all studies reported at least one outcome of interest, but longer follow-up was necessary to fully observe outcomes. Therefore, at least one year of follow-up is considered necessary to demonstrate efficacy. Setting Patients with cancer who are undergoing radiotherapy or chemotherapy are managed by oncologists in an outpatient clinical setting. Study Selection Criteria Methodologically credible studies were selected using the following principles:




Studies with duplicative or overlapping populations were excluded. In a 2005 Cochrane review,62, which was updated in 2012,63, and in 2018, Bennett et al identified 19 randomized and quasi-randomized trials (total N=2286 patients) comparing outcomes following radiotherapy with and without HBOT in patients with solid tumors (see Table 30). The latest trial identified in the Cochrane search was published in 1999. Reviewers did not find any ongoing RCTs in this area. Results from the review reported that HBOT given with radiotherapy might be useful in tumor control in head and neck cancer. However, reviewers expressed caution






because significant adverse events, such as severe radiation tissue injury (relative risk, 2.3; p<0.001) and seizures (relative risk, 6.8; p=0.03) occurred more frequently in patients treated with HBOT. Table 30. Systematic Reviews of Trials Assessing HBOT for Tumor Sensitization During Cancer Treatment with Radiotherapy

Study (Year)

Literature Search



Sep 2017 19, some including multiple cancer sites

· Head and neck: 10 trials · Uterine: 7 trials · Urinary bladder: 5 trials · Bronchus: 1 trial · Rectum: 1 trial · Brain: 1 trial · Esophagus: 1 trial

2286 RCT and quasi-RCT

Head and neck: · 1-y mortality: RR=0.8 (p=0.03) · 5-year mortality: RR=0.8 (p=0.03) · 5-y recurrence: RR=0.8 (p=0.01) Uterine: · 2-y recurrence: RR=0.6 (p=04)

HBOT: hyperbaric oxygen therapy; RCT: randomized controlled trial; RR: relative risk. In an RCT of 32 patients, Heys et al (2006) found no increase in 5-year survival for patients treated with HBOT to increase tumor vascularity before chemotherapy for locally advanced breast carcinoma.64, Section Summary: Tumor Sensitization During Cancer Treatment: Radiotherapy or Chemotherapy A Cochrane review on the use of HBOT with radiotherapy and an RCT on the use of HBOT with chemotherapy were identified. While the Cochrane review found improvements in tumor control in patients with head and neck cancer, the adverse events accompanying HBOT treatment (eg, radiation tissue injury, seizures) were significant. The RCT did not find a significant difference in survival in cancer patients who received HBOT before chemotherapy. Other Indications For the indications listed below, literature searches did could not identify sufficient evidence to support the use of HBOT. Since 2000, there have been no published controlled trials or large case series (ie, ³25 patients) assessing:

• bone grafts; • carbon tetrachloride poisoning, acute; • cerebrovascular disease, acute (thrombotic or embolic) or chronic; • fracture healing; • hydrogen sulfide poisoning; • intra-abdominal and intracranial abscesses; • lepromatous leprosy; • meningitis; • pseudomembranous colitis (antimicrobial agent-induced colitis); • radiation myelitis; • sickle cell crisis and/or hematuria; • amyotrophic lateral sclerosis; • retinal artery insufficiency, acute; • retinopathy, adjunct to scleral buckling procedures in patients with sickle cell peripheral

retinopathy and retinal detachment; • pyoderma gangrenosum; • compromised skin grafts and flaps; • brown recluse spider bites;






• spinal cord injury; • refractory mycoses; • acute peripheral arterial insufficiency; • in vitro fertilization; • amyotrophic lateral sclerosis; or • mental illness.

SUMMARY OF EVIDENCE

For individuals with wounds, burns or infections who receive topical HBOT, the evidence includes a systematic review, case series, and an RCT. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. The systematic review identified 3 RCTs including patients with sacral pressure ulcers, ischial pressure ulcers, and refractory venous ulcers. All trials reported that healing improved significantly after HBOT than after standard of care. Pooling of results was not possible due to heterogeneity in patient populations and treatment regimens. The single small RCT (N=28) was not included in the review and the uncontrolled studies do not provide sufficient data that topical HBOT is efficacious. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with wounds, burns or infections who receive topical HBOT, the evidence includes a systematic review, case series, and a randomized controlled trial (RCT). Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. The systematic review identified 3 RCTs including patients with sacral pressure ulcers, ischial pressure ulcers, and refractory venous ulcers. All trials reported that healing improved significantly after HBOT than after standard of care. Pooling of results was not possible due to heterogeneity in patient populations and treatment regimens. The single small RCT (N=28) was not included in the review and the uncontrolled studies do not provide sufficient data that topical HBOT is efficacious. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with chronic diabetic ulcers who receive systemic HBOT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms and change in disease status. Meta-analyses of RCTs found significantly higher diabetic ulcer healing rates with HBOT than with control conditions. One of the 2 meta-analyses found that HBOT was associated with a significantly lower rate of major amputation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. For individuals with carbon monoxide poisoning who receive systemic HBOT, the evidence includes RCTs and a systematic review. Relevant outcomes are overall survival and symptoms. A meta-analysis in a Cochrane review of low-quality RCT data did not find HBOT to be associated with a significantly lower risk of neurologic deficits after carbon monoxide poisoning. The evidence is insufficient to determine the effects of the technology on health outcomes. However, clinical input obtained in 2010 and guidelines from the Undersea and Hyperbaric Medical Society and the 10th European Consensus Conference on Hyperbaric Medicine support HBOT for the treatment of acute carbon monoxide poisoning. Thus, based on clinical input and guideline support, this indication may be considered medically necessary. For individuals with radionecrosis, osteoradionecrosis, or treatment of irradiated jaw who receive systemic HBOT, the evidence includes RCTs and a systematic review. Relevant outcomes are




symptoms and change in disease status. A meta-analysis in a Cochrane review of RCTs found evidence that HBOT improved radionecrosis and osteoradionecrosis outcomes and resulted in better outcomes before tooth extraction in an irradiated jaw. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. For individuals with chronic refractory osteomyelitis who receive systemic HBOT, the evidence includes case series. Relevant outcomes are symptoms and change in disease status. The case series reported high rates of successful outcomes (no drainage, pain, tenderness, or cellulitis) in patients with chronic refractory osteomyelitis treated with HBOT. However, controlled studies are needed to determine conclusively the impact of HBOT on health outcomes compared with other interventions. The evidence is insufficient to determine the effects of the technology on health outcomes. However, clinical input obtained in 2010 and Undersea and Hyperbaric Medical Society guidelines support HBOT for the treatment of chronic refractory osteomyelitis. Thus, based on clinical input and guideline support, this indication may be considered medically necessary. For individuals with acute thermal burns who receive systemic HBOT, the evidence includes a systematic review of 2 RCTs. Relevant outcomes are overall survival, symptoms, and change in disease status. Only 2 RCTs were identified, and both were judged to have poor methodologic quality. Evidence from well-conducted controlled trials is needed. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with acute surgical and traumatic wounds who receive systemic HBOT, the evidence includes RCTs, controlled nonrandomized studies, and systematic reviews. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. There was considerable heterogeneity across the 4 RCTs identified (eg, patient population, comparison group, treatment regimen, outcomes). This heterogeneity prevented pooling of trial findings and limits the ability to conclude the impact of HBOT on health outcomes for patients with acute surgical and traumatic wounds. Additional evidence from high-quality RCTs is needed. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with bisphosphonate-related osteonecrosis of the jaw who receive systemic HBOT, the evidence includes an RCT. Relevant outcomes are symptoms and change in disease status. The RCT was unblinded and reported initial benefits at 3-month follow-up; however, there were no significant benefits of HBOT for most health outcomes compared with standard care in the long-term (6 months to 2 years). The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with necrotizing soft tissue infections who receive systemic HBOT, the evidence includes systematic reviews and a retrospective cohort study. Relevant outcomes are overall survival, symptoms, and change in disease status. A Cochrane review did not identify any RCTs. Another systematic review identified a retrospective cohort study, which did not find better outcomes after HBOT than after standard care without HBOT in patients with necrotizing soft tissue infections. The evidence is insufficient to determine the effects of the technology on health outcomes.




For individuals with acute coronary syndrome who receive systemic HBOT, the evidence includes RCTs and a systematic review. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. A Cochrane review identified 6 RCTs. There were 2 pooled analyses, one found significantly lower rates of death with HBOT and the other reported inconsistent results in left ventricular function. Additional RCT data are needed. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with acute ischemic stroke who receive systemic HBOT, the evidence includes RCTs and a systematic review. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. Cochrane reviewers could only pool data for a single outcome (mortality at 3-6 months), and for that outcome, there was no significant difference between active and sham HBOT treatments. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with motor dysfunction associated with stroke who receive systemic HBOT, the evidence includes an RCT. Relevant outcomes are symptoms and functional outcomes. The RCT, which used a crossover design, found better outcomes with HBOT at 2 months than with delayed treatment. However, the trial had a number of methodologic limitations (eg, lack of patient blinding, heterogeneous population, high dropout rate) that make it difficult to evaluate the efficacy of HBOT. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with Bell palsy who receive systemic HBOT, the evidence includes a systematic review. Relevant outcomes are symptoms, change in disease status, and functional outcomes. A Cochrane review did not identify any RCTs meeting selection criteria; the single RCT found did not have a blinded outcome assessment. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with traumatic brain injury who receive systemic HBOT, the evidence includes RCTs and systematic reviews. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. RCTs were heterogenous regarding intervention protocols, patient populations, and outcomes reported. Systematic reviews conducted pooled analyses only on a minority of the published RCTs, and these findings were inconsistent. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with inflammatory bowel disease who receive systemic HBOT, the evidence includes an RCT, observational studies, and a systematic review. Relevant outcomes are symptoms, change in disease status and functional outcomes. One small RCT has been published, and this trial did not find a significant improvement in health outcomes when HBOT was added to standard medical therapy. A systematic review including the RCT and observational studies found a high rate of bias in the literature due to attrition and reporting bias. The evidence is insufficient to determine the effects of the technology on health outcomes. A Cochrane review of RCTs had mixed findings from studies that included individuals with tinnitus. Some outcomes (ie, improvement in hearing of all frequencies, >25% return of hearing) were better with HBOT than with a control intervention, but more than 50% return of hearing did not differ significantly between groups. There was important variability in the patients enrolled in the studies. A subsequent systematic review had similarly limited conclusions due to the inclusion




of non-randomized studies. One RCT included in this review included patients with ISSNHL and found no differences in HBOT treatment compared with steroid injections in mean hearing thresholds at 0.25, 0.5, 1, and 4 kHz; however, a significant difference was detected at the 2-kHz level. Nonrandomized studies of HBOT used as adjunctive therapy did not support incremental value. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with delayed-onset muscle soreness who receive systemic HBOT, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms and functional outcomes. A Cochrane review of RCTs found worse short-term pain outcomes with HBOT than with control and no difference in longer term pain or other outcomes (eg, swelling). The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with autism spectrum disorder who receive systemic HBOT, the evidence includes an RCT and a systematic review. Relevant outcomes are symptoms and functional outcomes. A Cochrane review identified a single RCT on HBOT for autism spectrum disorder and this trial did not find significantly better parental-assessed or clinician-assessed outcomes with HBOT compared with sham. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with cerebral palsy who receive systemic HBOT, the evidence includes 2 RCTs and an observational study. Relevant outcomes are symptoms and functional outcomes. One RCT was stopped early due to futility, and the other did not find significantly better outcomes with HBOT than with a sham intervention. The observational study focused on sleep disorders in children with cerebral palsy and reported improvements with the HBOT treatment. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with vascular dementia who receive systemic HBOT, the evidence includes an RCT and a systematic review. Relevant outcomes are symptoms and functional outcomes. The Cochrane review identified only a single RCT with methodologic limitations. Well-conducted controlled trials are needed. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with radiotherapy adverse events who receive systemic HBOT, the evidence includes RCTs, nonrandomized comparator trials, case series, and systematic reviews. Relevant outcomes are symptoms and functional outcomes. Two systematic reviews were identified, but pooled analyses were not possible due to heterogeneity in treatment regimens and outcomes measured. One systematic review concluded that more RCTs would be needed. The 2 RCTs identified had inconsistent findings. One reported no short-term benefit with HBOT, but some benefits 12 months after radiotherapy; the other did not find a significant benefit of HBOT at 12-month follow-up. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with idiopathic femoral neck necrosis who receive systemic HBOT, the evidence includes an RCT. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The RCT, which had a small sample, only reported short-term (ie, 6-week) outcomes. Larger well-conducted RCTs reporting longer term outcomes are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.




For individuals with a migraine who receive systemic HBOT, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The Cochrane review conducted a pooled analysis including 3 of the 11 trials. Meta-analysis of these 3 RCTs found significantly greater relief of migraine symptoms with HBOT than with a comparator intervention within 45 minutes of treatment. Longer term data are needed. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with herpes zoster who receive systemic HBOT, the evidence includes an RCT. Relevant outcomes are symptoms and change in disease status. The RCT was unblinded and only reported short-term (ie, 6-week) outcomes. Additional well-conducted RCTs with longer follow-up are needed. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with fibromyalgia who receive systemic HBOT, the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Only 2 RCTs were identified, and both reported positive effects of HBOT on tender points and pain. However, the trials had relatively small samples and methodologic limitations (eg, quasi-randomization, no or uncertain sham control for a condition with subjective outcomes susceptible to a placebo effect). Moreover, the HBOT protocols varied. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with multiple sclerosis who receive systemic HBOT, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms and functional outcomes. A Cochrane review of RCTs did not find a significant difference in Expanded Disability Status Scale scores when patients with multiple sclerosis were treated with HBOT vs a comparator intervention. The evidence is insufficient to determine the effects of the technology on health outcomes. For individuals with cancer and are undergoing chemotherapy who receive systemic HBOT, the evidence includes an RCT and a systematic review. Relevant outcomes are overall survival and change in disease status. While the systematic review reported improvements in tumor control in patients with head and neck cancer who received HBOT, the adverse events accompanying the treatment (eg, radiation tissue injury, seizures) were significant. The single RCT did not find a significant difference in survival for cancer patients who received HBOT before chemotherapy compared with usual care. The evidence is insufficient to determine the effects of the technology on health outcomes.

CLINICAL INPUT FROM PHYSICIAN MEDICAL SOCIETIES AND ACADEMIC MEDICAL CENTERS

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. In response to requests, input was received through 6 physician specialty societies and 5 academic medical centers while this policy was under review in 2010. The clinical input varied depending on the condition. There was universal agreement that topical HBOT and systemic HBOT for autism spectrum disorder and headache/migraine are investigational. There was also wide support for changing acute carbon monoxide poisoning, compromised skin grafts or flaps,




chronic refractory osteomyelitis, and necrotizing soft tissue infections to the list of medically necessary indications for HBOT. Several reviewers acknowledged that there is a paucity of clinical trials on HBOT for compromised skin grafts/flaps, necrotizing soft tissue infections, and chronic refractory osteomyelitis. These reviewers commented on the support from basic science, animal studies, and retrospective case series, as well as lack of effective alternative treatments for these conditions. Based on the available evidence and clinical input, acute carbon monoxide poisoning and chronic refractory osteomyelitis were changed in 2010 to medically necessary indications for HBOT. However, despite the clinical input and given the limited published evidence, compromised skin grafts and flaps and necrotizing soft tissue infections are still considered investigational.

PRACTICE GUIDELINES AND POSITION STATEMENTS Diabetic Foot Conditions Undersea and Hyperbaric Medical Society In 2015, the Undersea and Hyperbaric Medical Society (UHMS) published guidelines on use of hyperbaric oxygen therapy (HBOT) for treating diabetic foot ulcers.65 Recommendations included:

• Suggest against using HBOT in patients with “Wagner Grade 2 or lower diabetic foot ulcers….”

• Suggest adding HBOT in patients with “Wagner Grade 3 or higher diabetic foot ulcers that have not shown significant improvement after 30 days of [standard of care] therapy….”

• Suggest “adding acute post-operative hyperbaric oxygen therapy to the standard of care” in patients with “Wagner Grade 3 or higher diabetic foot ulcers” who have just had foot surgery related to their diabetic ulcers.

Infectious Disease Society of America In 2012, the Infectious Disease Society of America published guidelines on the diagnosis and treatment of diabetic foot infections.66 The guidelines stated that “for selected diabetic foot wounds that are slow to heal, clinicians might consider using hyperbaric oxygen therapy (strength of evidence: strong; quality of evidence: moderate).” Society of Vascular Surgery et al In 2016, the Society of Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine published guidelines on the management of the diabetic foot.67 According to the guidelines, for diabetic foot ulcers that fail to demonstrate improvement (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, adjunctive therapy such as HBOT is recommended (grade 1B). Also, for diabetic foot ulcers with adequate perfusion that fail to respond to 4 to 6 weeks of conservative management, HBOT is suggested (grade 2B). Other Conditions Underseas and Hyperbaric Medical Society UHMS published indications that the society considered appropriate for HBOT; the latest update was published in 2014 (13th edition).68 These indications are as follows:

1. Air or Gas Embolism 2. Carbon Monoxide Poisoning and carbon monoxide complicated by cyanide poisoning 3. Clostridial Myositis and Myonecrosis (Gas Gangrene) 4. Crush Injury, Compartment Syndrome and Other Acute Traumatic Ischemias 5. Decompression Sickness 6. Arterial Insufficiencies




7. Severe Anemia 8. Intracranial Abscess 9. Necrotizing Soft Tissue Infections 10. Osteomyelitis (Refractory) 11. Delayed Radiation Injury (Soft Tissue and Bony Necrosis) 12. Compromised Grafts and Flaps 13. Acute Thermal Burn Injury 14. Idiopathic Sudden Sensorineural Hearing Loss.

UHMS has also published position statements that concluded there was insufficient evidence to recommend topical HBOT for chronic wounds (2005),69 multiple sclerosis,70 and autism spectrum disorder (2009).71 American Academy of Otolaryngology – Head and Neck Surgery In 2012, the American Academy of Otolaryngology-Head and Neck Surgery published a clinical guideline on treatment of sudden hearing loss.72 The guideline includes a statement that HBOT may be considered a treatment option for patients who present within 3 months of a diagnosis of idiopathic sudden sensorineural hearing loss (ISSNHL). The document states, “Although HBOT is not widely available in the United States and is not recognized by many U.S. clinicians as an intervention for ISSNHL, the panel felt that the level of evidence for hearing improvement, albeit modest and imprecise, was sufficient to promote greater awareness of HBOT as an intervention for ISSNHL.” (Grade B recommendation, based on systematic review of RCTs with methodological limitations.) Tenth European Consensus Conference on Hyperbaric Medicine The 10th European Consensus Conference on Hyperbaric Medicine (ECHM) convened in April 2016 to update HBOT indication recommendations.73 Evidence was assessed using a modified GRADE system with the DELPHI system for consensus evaluation. Table 31 presents the updated recommendations: Table 31. Recommendations on Hyperbaric Medicine

Condition SOR LOE Carbon monoxide poisoning Strong Moderate Open fractures with crush injury Strong Moderate Prevention of osteoradionecrosis Strong Moderate Osteoradionecrosis (mandible) Strong Moderate Soft tissue radionecrosis (cystitis, proctitis) Strong Moderate Decompression illness Strong Low Gas embolism Strong Low Anaerobic or mixed bacterial infection Strong Low Sudden deafness Strong Moderate Diabetic foot lesions Weak Moderate Femoral head necrosis Weak Moderate Compromised skin grafts and musculocutaneous flaps Weak Low Central retinal artery occlusion Weak Low Crush injury without fracture Weak Low Osteoradionecrosis (other than mandible) Weak Low Radio-induced lesions of soft tissues Weak Low Radio-induced lesions of soft tissues (preventive) Weak Low Ischemic ulcers Weak Low Refractory chronic osteomyelitis Weak Low Burns, second degree, >20% body surface area Weak Low Pneumatosis cystoides intestinalis Weak Low




Condition SOR LOE Neuroblastoma, stage IV Weak Low Brain injury in highly selected patients Neutral Low Radio-induced lesions of larynx Neutral Low Radio-induced lesions of central nervous system Neutral Low Post-vascular procedure reperfusion syndrome Neutral Low Limb replantation Neutral Low Selected non-healing wounds, secondary to systemic process Neutral Low Sickle cell disease Neutral Low Interstitial cystitis Neutral Low

Adapted from Mathieu et al (2017).69 LOE: level of evidence; SOR: strength of recommendation.

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS Not applicable.

ONGOING AND UNPUBLISHED CLINICAL TRIALS Some currently unpublished trials that might influence this review are listed in Table 32. Table 32. Summary of Key Trials

NCT No. Trial Name Planned

Enrollment Completion

Date Ongoing NCT01659723 Radiation Induced Cystitis Treated With Hyperbaric Oxygen - A

Randomized Controlled Trial (RICH-ART) 80 Dec 2017

NCT03147352 Pro-Treat – Prognosis and Treatment of Necrotizing Soft Tissue Infections: a Prospective Cohort Study

310 Jan 2018

NCT02089594 Hyperbaric Oxygen Therapy Treatment of Chronic Mild Traumatic Brain Injury (mTBI)/Persistent Post-Concussion Syndrome (PCCS)

59 Mar 2019

NCT02714465 Treatment of Adverse Radiation Effects after Gamma Knife Radiosurgery (GKS) by Hyperbaric Oxygen Therapy (HBO)

65 May 2019

NCT03325959 Hyperbaric Oxygen versus Standard Pharmaceutical Therapies for Fibromyalgia Syndrome – Prospective, Randomized, Crossover Clinical Trial

70 Nov 2019

NCT00596180 Hyperbaric Oxygen Therapy and SPECT Brain Imaging in Carbon Monoxide Poisoning

40 Dec 2019

NCT01002209 Postoperative Hyperbaric Oxygen Treatments to Reduce Complications in Diabetic Patients Undergoing Vascular Surgery (HODiVA)

112 Oct 2020

NCT01847755 Phase 1-2 Study of Hyperbaric Treatment of Traumatic Brain Injury

100 Dec 2020

Unpublished NCT02085330 Hyperbaric Oxygen Therapy for Mild Cognitive Impairment 60 Feb 2017

(unknown) NCT: national clinical trial.




CODING The following codes for treatment and procedures applicable to this policy are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. CPT/HCPCS 99183 Physician or other qualified health care provider attendance and supervision of

hyperbaric oxygen therapy, per session A4575 Topical hyperbaric oxygen chamber, disposable G0277 Hyperbaric oxygen under pressure, full body chamber, per 30 minute interval

Topical Hyperbaric Oxygen

HCPCS code A4575 is used to describe a disposable topical hyperbaric oxygen appliance that creates a "chamber" around the wound area which is pressurized with "hyperbaric" oxygen. Conventional oxygen tanks, typically gas, are used to supply the oxygen.

ICD-10 DiagnosesA42.2 A42.89 A42.9 A43.1 A43.8 A43.9 A48.0 B36.0 B36.1 B36.2 B36.3 B36.8 B36.9 B37.0 B37.2 B37.3 B37.41 B37.42 B37.49 B37.83 B46.0 B46.1 B46.2 B46.3 B46.4 B46.5 B46.8 B46.9 B47.1

B47.9 B48.3 B48.8 B49 B78.1 D62 E08.52 E08.59 E08.620 E08.621 E08.622 E08.628 E09.59 E09.620 E09.621 E09.622 E09.628 E10.52 E10.59 E10.620 E10.621 E10.622 E10.628 E11.52 E11.59 E11.620 E11.621 E11.622 E11.628

E13.52 E13.59 E13.620 E13.621 E13.622 E13.628 G06.0 H34.11 H34.12 H34.13 H70.201 H70.202 H70.203 H70.209 H70.211 H70.212 H70.213 H70.221 H70.222 H70.223 H70.229 I70.231 I70.232 I70.233 I70.234 I70.235 I70.238 I70.239 I70.241

I70.242 I70.243 I70.244 I70.245 I70.248 I70.249 I70.25 I70.331 I70.332 I70.333 I70.334 I70.335 I70.338 I70.339 I70.341 I70.342 I70.343 I70.344 I70.345 I70.348 I70.349 I70.35 I70.431 I70.432 I70.433 I70.434 I70.435 I70.438 I70.439






I87.9 I99.9 L08.0 L08.1 L08.81 L08.82 L08.89 L08.9 L88 L89.001 L89.002 L89.003 L89.004 L89.006 L89.010 L89.011 L89.012 L89.013 L89.014 L89.016 L89.020 L89.021 L89.022 L89.023 L89.024 L89.026 L89.029 L89.101 L89.102 L89.103 L89.104 L89.106 L89.110 L89.111 L89.112 L89.113 L89.114 L89.116 L89.120 L89.121 L89.122 L89.123 L89.124 L89.126 L89.130 L89.131 L89.132 L89.133

L89.134 L89.136 L89.140 L89.141 L89.142 L89.143 L89.144 L89.146 L89.150 L89.151 L89.152 L89.153 L89.154 L89.156 L89.206 L89.210 L89.211 L89.212 L89.213 L89.214 L89.216 L89.220 L89.221 L89.222 L89.223 L89.224 L89.226 L89.306 L89.310 L89.311 L89.312 L89.313 L89.314 L89.316 L89.320 L89.321 L89.322 L89.323 L89.324 L89.326 L89.41 L89.42 L89.43 L89.44 L89.45 L89.46 L89.506 L89.510




L97.921 L97.922 L97.923 L97.924 L97.925 L97.926 L97.928 L97.929 L98.0 L98.411 L98.412 L98.413 L98.414 L98.415 L98.416 L98.418 L98.419 L98.421 L98.422 L98.423 L98.424 L98.425 L98.426 L98.428 L98.429 L98.491 L98.492 L98.493 L98.494 L98.495 L98.496 L98.498 L98.499 M27.0 M27.2 M27.8 M62.9 M63.80 M63.811 M63.812 M63.821 M63.822 M63.831 M63.832 M63.841 M63.842 M63.851 M63.852




M63.861 M63.862 M63.871 M63.872 M63.88 M63.89 M72.6 M79.A11 M79.A12 M79.A19 M79.A21 M79.A22 M79.A3 M79.A9 M86.30 M86.311 M86.312 M86.321 M86.322 M86.331 M86.332 M86.341 M86.342 M86.351 M86.352 M86.361 M86.362 M86.371 M86.372 M86.38 M86.39 M86.40 M86.411 M86.412 M86.421 M86.422 M86.431 M86.432 M86.441 M86.442 M86.451 M86.452 M86.461 M86.462 M86.471 M86.472 M86.48 M86.49

M86.50 M86.511 M86.512 M86.521 M86.522 M86.531 M86.532 M86.541 M86.542 M86.549 M86.551 M86.552 M86.561 M86.562 M86.571 M86.572 M86.58 M86.59 M86.60 M86.611 M86.612 M86.621 M86.622 M86.631 M86.632 M86.641 M86.642 M86.651 M86.652 M86.661 M86.662 M86.671 M86.672 M86.68 M86.69 M86.8X0 M86.8X1 M86.8X2 M86.8X3 M86.8X4 M86.8X5 M86.8X6 M86.8X7 M86.8X8 M86.8X9 M90.811 M90.812 M90.821

M90.822 M90.831 M90.832 M90.841 M90.842 M90.851 M90.852 M90.861 M90.862 M90.871 M90.872 M90.88 M90.89 N30.40 N30.41 S07.0XXA S07.0XXD S07.0XXS S07.1XXA S07.1XXD S07.1XXS S07.8XXA S07.8XXD S07.8XXS S07.9XXA S07.9XXD S07.9XXS S17.0XXA S17.0XXD S17.0XXS S17.8XXA S17.8XXD S17.8XXS S17.9XXA S17.9XXD S17.9XXS S28.0XXA S28.0XXD S28.0XXS S35.511A S35.511D S35.511S S35.512A S35.512D S35.512S S38.001A S38.001D S38.001S

S38.002A S38.002D S38.002S S38.01XA S38.01XD S38.01XS S38.02XA S38.02XD S38.02XS S38.03XA S38.03XD S38.03XS S38.1XXA S38.1XXD S38.1XXS S45.001A S45.001D S45.001S S45.002A S45.002D S45.002S S45.011A S45.011D S45.011S S45.012A S45.012D S45.012S S45.091A S45.091D S45.091S S45.092A S45.092D S45.092S S45.101A S45.101D S45.101S S45.102A S45.102D S45.102S S45.111A S45.111D S45.111S S45.112A S45.112D S45.112S S45.191A S45.191D S45.191S

S45.192A S45.192D S45.192S S45.201A S45.201D S45.201S S45.202A S45.202D S45.202S S45.211A S45.211D S45.211S S45.212A S45.212D S45.212S S45.291A S45.291D S45.291S S45.292A S45.292D S45.292S S45.301A S45.301D S45.301S S45.302A S45.302D S45.302S S45.311A S45.311D S45.311S S45.312A S45.312D S45.312S S45.391A S45.391D S45.391S S45.392A S45.392D S45.392S S45.801A S45.801D S45.801S S45.802A S45.802D S45.802S S45.811A S45.811D S45.811S

S45.812A S45.812D S45.812S S45.891A S45.891D S45.891S S45.892A S45.892D S45.892S S45.899A S45.899D S45.899S S45.901A S45.901D S45.901S S45.902A S45.902D S45.902S S45.911A S45.911D S45.911S S45.912A S45.912D S45.912S S45.919A S45.919D S45.919S S45.991A S45.991D S45.991S S45.992A S45.992D S45.992S S47.1XXA S47.1XXD S47.1XXS S47.2XXA S47.2XXD S47.2XXS S47.9XXA S47.9XXD S47.9XXS S55.001A S55.001D S55.001S S55.002A S55.002D S55.002S





S55.291A S55.291D S55.291S S55.292A S55.292D S55.292S S55.801A S55.801D S55.801S S55.802A S55.802D S55.802S S55.811A S55.811D S55.811S S55.812A S55.812D S55.812S S55.891A S55.891D S55.891S S55.892A S55.892D S55.892S S55.899A S55.899D S55.899S S55.901A S55.901D S55.901S S55.902A S55.902D S55.902S S55.911A S55.911D S55.911S S55.912A S55.912D S55.912S S55.991A S55.991D S55.991S S55.992A S55.992D S55.992S S57.01XA S57.01XD S57.01XS

S57.02XA S57.02XD S57.02XS S57.81XA S57.81XD S57.81XS S57.82XA S57.82XD S57.82XS S65.001A S65.001D S65.001S S65.002A S65.002D S65.002S S65.011A S65.011D S65.011S S65.012A S65.012D S65.012S S65.091A S65.091D S65.091S S65.092A S65.092D S65.092S S65.101A S65.101D S65.101S S65.102A S65.102D S65.102S S65.111A S65.111D S65.111S S65.112A S65.112D S65.112S S65.191A S65.191D S65.191S S65.192A S65.192D S65.192S S65.201A S65.201D S65.201S







S65.811A S65.811D S65.811S S65.812A S65.812D S65.812S S65.891A S65.891D S65.891S S65.892A S65.892D S65.892S S65.901A S65.901D S65.901S S65.902A S65.902D S65.902S S65.911A S65.911D S65.911S S65.912A S65.912D S65.912S S65.991A S65.991D S65.991S S65.992A S65.992D S65.992S S65.999A S65.999D S65.999S S67.01XA S67.01XD S67.01XS S67.02XA S67.02XD S67.02XS S67.190A S67.190D S67.190S S67.191A S67.191D S67.191S S67.192A S67.192D S67.192S

S67.193A S67.193D S67.193S S67.194A S67.194D S67.194S S67.195A S67.195D S67.195S S67.196A S67.196D S67.196S S67.197A S67.197D S67.197S S67.198A S67.198D S67.198S S67.21XA S67.21XD S67.21XS S67.22XA S67.22XD S67.22XS S67.31XA S67.31XD S67.31XS S67.32XA S67.32XD S67.32XS S67.41XA S67.41XD S67.41XS S67.42XA S67.42XD S67.42XS S67.91XA S67.91XD S67.91XS S67.92XA S67.92XD S67.92XS S75.001A S75.001D S75.001S S75.002A S75.002D S75.002S


S75.912A S75.912D S75.912S S75.991A S75.991D S75.991S S75.992A S75.992D S75.992S S77.01XA S77.01XD S77.01XS S77.02XA S77.02XD S77.02XS S77.11XA S77.11XD S77.11XS S77.12XA S77.12XD S77.12XS S85.001A S85.001D S85.001S S85.002A S85.002D S85.002S S85.011A S85.011D S85.011S S85.012A S85.012D S85.012S S85.019A S85.019D S85.019S S85.091A S85.091D S85.091S S85.092A S85.092D S85.092S S85.131A S85.131D S85.131S S85.132A S85.132D S85.132S


S85.811A S85.811D S85.811S S85.891A S85.891D S85.891S S85.892A S85.892D S85.892S S85.901A S85.901D S85.901S S85.902A S85.902D S85.902S S85.911A S85.911D S85.911S S85.912A S85.912D S85.912S S85.991A S85.991D S85.991S S85.992A S85.992D S85.992S S87.01XA S87.01XD S87.01XS S87.02XA S87.02XD S87.02XS S87.81XA S87.81XD S87.81XS S87.82XA S87.82XD S87.82XS S95.001A S95.001D S95.001S S95.002A S95.002D S95.002S S95.011A S95.011D S95.011S





S95.802A S95.802D S95.802S S95.809A S95.809D S95.809S S95.811A S95.811D S95.811S S95.812A S95.812D S95.812S S95.891A S95.891D S95.891S S95.892A S95.892D S95.892S S95.901A S95.901D S95.901S S95.902A S95.902D S95.902S S95.911A S95.911D S95.911S S95.912A S95.912D S95.912S S95.991A S95.991D S95.991S S95.992A S95.992D S95.992S S97.01XA S97.01XD S97.01XS S97.02XA S97.02XD S97.02XS S97.101A S97.101D S97.101S S97.102A S97.102D S97.102S

S97.111A S97.111D S97.111S S97.112A S97.112D S97.112S S97.121A S97.121D S97.121S S97.122A S97.122D S97.122S S97.81XA S97.81XD S97.81XS S97.82XA S97.82XD S97.82XS T14.8 T20.20XA T20.20XD T20.20XS T20.211A T20.211D T20.211S T20.212A T20.212D T20.212S T20.22XA T20.22XD T20.22XS T20.23XA T20.23XD T20.23XS T20.24XA T20.24XD T20.24XS T20.25XA T20.25XD T20.25XS T20.26XA T20.26XD T20.26XS T20.27XA T20.27XD T20.27XS T20.29XA T20.29XD

T20.29XS T20.30XA T20.30XD T20.30XS T20.311A T20.311D T20.311S T20.312A T20.312D T20.312S T20.319A T20.319D T20.319S T20.32XA T20.32XD T20.32XS T20.33XA T20.33XD T20.33XS T20.34XA T20.34XD T20.34XS T20.35XA T20.35XD T20.35XS T20.36XA T20.36XD T20.36XS T20.37XA T20.37XD T20.37XS T20.39XA T20.39XD T20.39XS T20.60XA T20.60XD T20.60XS T20.611A T20.611D T20.611S T20.612A T20.612D T20.612S T20.62XA T20.62XD T20.62XS T20.63XA T20.63XD

T20.63XS T20.64XA T20.64XD T20.64XS T20.65XA T20.65XD T20.65XS T20.66XA T20.66XD T20.66XS T20.67XA T20.67XD T20.67XS T20.69XA T20.69XD T20.69XS T20.70XA T20.70XD T20.70XS T20.711A T20.711D T20.711S T20.712A T20.712D T20.712S T20.72XA T20.72XD T20.72XS T20.73XA T20.73XD T20.73XS T20.74XA T20.74XD T20.74XS T20.75XA T20.75XD T20.75XS T20.76XA T20.76XD T20.76XS T20.77XA T20.77XD T20.77XS T20.79XA T20.79XD T20.79XS T21.20XA T21.20XD

T21.20XS T21.21XA T21.21XD T21.21XS T21.22XA T21.22XD T21.22XS T21.23XA T21.23XD T21.23XS T21.24XA T21.24XD T21.24XS T21.25XA T21.25XD T21.25XS T21.26XA T21.26XD T21.26XS T21.27XA T21.27XD T21.27XS T21.29XA T21.29XD T21.29XS T21.30XA T21.30XD T21.30XS T21.31XA T21.31XD T21.31XS T21.32XA T21.32XD T21.32XS T21.33XA T21.33XD T21.33XS T21.34XA T21.34XD T21.34XS T21.35XA T21.35XD T21.35XS T21.36XA T21.36XD T21.36XS T21.37XA T21.37XD




T21.37XS T21.39XA T21.39XD T21.39XS T21.60XA T21.60XD T21.60XS T21.61XA T21.61XD T21.61XS T21.62XA T21.62XD T21.62XS T21.63XA T21.63XD T21.63XS T21.64XA T21.64XD T21.64XS T21.65XA T21.65XD T21.65XS T21.66XA T21.66XD T21.66XS T21.67XA T21.67XD T21.67XS T21.69XA T21.69XD T21.69XS T21.70XA T21.70XD T21.70XS T21.71XA T21.71XD T21.71XS T21.72XA T21.72XD T21.72XS T21.73XA T21.73XD T21.73XS T21.74XA T21.74XD T21.74XS T21.75XA T21.75XD

T21.75XS T21.76XA T21.76XD T21.76XS T21.77XA T21.77XD T21.77XS T21.79XA T21.79XD T21.79XS T22.20XA T22.20XD T22.20XS T22.211A T22.211D T22.211S T22.212A T22.212D T22.212S T22.221A T22.221D T22.221S T22.222A T22.222D T22.222S T22.231A T22.231D T22.231S T22.232A T22.232D T22.232S T22.241A T22.241D T22.241S T22.242A T22.242D T22.242S T22.251A T22.251D T22.251S T22.252A T22.252D T22.252S T22.261A T22.261D T22.261S T22.262A T22.262D

T22.262S T22.291A T22.291D T22.291S T22.292A T22.292D T22.292S T22.299A T22.299D T22.299S T22.30XA T22.30XD T22.30XS T22.311A T22.311D T22.311S T22.312A T22.312D T22.312S T22.321A T22.321D T22.321S T22.322A T22.322D T22.322S T22.331A T22.331D T22.331S T22.332A T22.332D T22.332S T22.341A T22.341D T22.341S T22.342A T22.342D T22.342S T22.351A T22.351D T22.351S T22.352A T22.352D T22.352S T22.361A T22.361D T22.361S T22.362A T22.362D

T22.362S T22.391A T22.391D T22.391S T22.392A T22.392D T22.392S T22.60XA T22.60XD T22.60XS T22.611A T22.611D T22.611S T22.612A T22.612D T22.612S T22.621A T22.621D T22.621S T22.622A T22.622D T22.622S T22.631A T22.631D T22.631S T22.632A T22.632D T22.632S T22.641A T22.641D T22.641S T22.642A T22.642D T22.642S T22.651A T22.651D T22.651S T22.652A T22.652D T22.652S T22.661A T22.661D T22.661S T22.662A T22.662D T22.662S T22.691A T22.691D

T22.691S T22.692A T22.692D T22.692S T22.70XA T22.70XD T22.70XS T22.711A T22.711D T22.711S T22.712A T22.712D T22.712S T22.721A T22.721D T22.721S T22.722A T22.722D T22.722S T22.731A T22.731D T22.731S T22.732A T22.732D T22.732S T22.739A T22.739D T22.739S T22.741A T22.741D T22.741S T22.742A T22.742D T22.742S T22.751A T22.751D T22.751S T22.752A T22.752D T22.752S T22.761A T22.761D T22.761S T22.762A T22.762D T22.762S T22.791A T22.791D

T22.791S T22.792A T22.792D T22.792S T22.799A T22.799D T22.799S T23.201A T23.201D T23.201S T23.202A T23.202D T23.202S T23.301A T23.301D T23.301S T23.302A T23.302D T23.302S T23.601A T23.601D T23.601S T23.602A T23.602D T23.602S T23.701A T23.701D T23.701S T23.702A T23.702D T23.702S T23.709A T23.709D T23.709S T24.201A T24.201D T24.201S T24.202A T24.202D T24.202S T24.301A T24.301D T24.301S T24.302A T24.302D T24.302S T24.601A T24.601D




T24.601S T24.602A T24.602D T24.602S T24.701A T24.701D T24.701S T24.702A T24.702D T24.702S T24.709A T24.709D T24.709S T26.21XA T26.21XD T26.21XS T26.22XA T26.22XD T26.22XS T26.41XA T26.41XD T26.41XS T26.42XA T26.42XD T26.42XS T26.71XA T26.71XD T26.71XS T26.72XA T26.72XD T26.72XS T31.0 T31.10 T31.11 T31.20 T31.21 T31.22 T31.30 T31.31 T31.32 T31.33 T31.40 T31.41 T31.42 T31.43 T31.44 T31.50 T31.51

T31.52 T31.53 T31.54 T31.55 T31.60 T31.61 T31.62 T31.63 T31.64 T31.65 T31.66 T31.70 T31.71 T31.72 T31.73 T31.74 T31.75 T31.76 T31.77 T31.80 T31.81 T31.82 T31.83 T31.84 T31.85 T31.86 T31.87 T31.88 T31.90 T31.91 T31.92 T31.93 T31.94 T31.95 T31.96 T31.97 T31.98 T31.99 T32.0 T32.0 T32.10 T32.11 T32.20 T32.21 T32.22 T32.30 T32.31 T32.32

T32.33 T32.40 T32.41 T32.42 T32.43 T32.44 T32.50 T32.51 T32.52 T32.53 T32.54 T32.55 T32.60 T32.61 T32.62 T32.63 T32.64 T32.65 T32.66 T32.70 T32.71 T32.72 T32.73 T32.74 T32.75 T32.76 T32.77 T32.80 T32.81 T32.82 T32.83 T32.84 T32.85 T32.86 T32.87 T32.88 T32.90 T32.91 T32.92 T32.93 T32.94 T32.95 T32.96 T32.97 T32.98 T32.99 T57.3X1A T57.3X1D

T57.3X1S T57.3X2A T57.3X2D T57.3X2S T57.3X3A T57.3X3D T57.3X3S T57.3X4A T57.3X4D T57.3X4S T58.01XA T58.01XD T58.01XS T58.02XA T58.02XD T58.02XS T58.03XA T58.03XD T58.03XS T58.04XA T58.04XD T58.04XS T58.11XA T58.11XD T58.11XS T58.12XA T58.12XD T58.12XS T58.13XA T58.13XD T58.13XS T58.14XA T58.14XD T58.14XS T58.2X1A T58.2X1D T58.2X1S T58.2X2A T58.2X2D T58.2X2S T58.2X3A T58.2X3D T58.2X3S T58.2X4A T58.2X4D T58.2X4S T58.8X1A T58.8X1D

T58.8X1S T58.8X2A T58.8X2D T58.8X2S T58.8X3A T58.8X3D T58.8X3S T58.8X4A T58.8X4D T58.8X4S T58.91XA T58.91XD T58.91XS T58.92XA T58.92XD T58.92XS T58.93XA T58.93XD T58.93XS T58.94XA T58.94XD T58.94XS T65.0X1A T65.0X1D T65.0X1S T65.0X2A T65.0X2D T65.0X2S T65.0X3A T65.0X3D T65.0X3S T65.0X4A T65.0X4D T65.0X4S T66.XXXA T66.XXXD T66.XXXS T70.20XA T70.20XD T70.20XS T70.29XA T70.29XD T70.29XS T70.3XXA T70.3XXD T70.3XXS T79.0XXA T79.0XXD

T79.0XXS T79.8XXA T79.8XXD T79.8XXS T79.9XXA T79.9XXD T79.9XXS T79.A0XA T79.A0XD T79.A0XS T79.A11A T79.A11D T79.A11S T79.A12A T79.A12D T79.A12S T79.A21A T79.A21D T79.A21S T79.A22A T79.A22D T79.A22S T79.A3XA T79.A3XD T79.A3XS T79.A9XA T79.A9XD T79.A9XS T80.0XXA T80.0XXD T80.0XXS T81.89XA T81.89XD T81.89XS T86.820 T86.821 T86.822 T86.828 T86.829 T87.0X1 T87.0X2 T87.0X9 T87.1X1 T87.1X2 T87.1X9 T87.2




REVISIONS 03-14-2011 Description section updated

In Policy section: Revised policy to current policy language from: "Covered Conditions: Benefits are available for hyperbaric oxygen (HBO) therapy that is administered in a chamber (whole body - single or multiple chamber). HBO therapy is a valuable adjunctive treatment to be used in combination with accepted standard therapeutic measures when loss of function, limb or life is threatened for the following conditions: 1. Acute carbon monoxide poisoning (986); smoke inhalation (987.9); cyanide poisoning (987.7 and 989.0). 2. Decompression sickness (993.2 – 993.3). 3. Cerebral arterial gas embolism (958.0 and 999.1). 4. Clostridial gas gangrene (040.0). 5. Acute traumatic peripheral ischemia (902.53, 903.01, 903.1, 904.0 and 904.41). 6. Crush injuries and suturing of severed limbs (925.1 - 929.9, 996.90 – 996.99). 7. Pyoderma gangrenosum (686.01) Note: The use of hyperbaric oxygen in any other type of cutaneous ulcer is not covered (problem wounds may be submitted for individual consideration). 8. Osteoradionecrosis as an adjunct to conventional treatment/osteoradionecrosis prevention and prophylactic treatments prior to dental extraction(s) involving areas of previously irradiated bone (526.89). 9. Soft tissue radionecrosis as an adjunct to conventional treatment (990). 10. Acute peripheral arterial insufficiency (444.21, 444.22, 444.81). 11. Preparation and preservation of compromised skin grafts (996.52). 12. Chronic refractory osteomyelitis, unresponsive to conventional medical and surgical management (730.00 – 730.29, 730.80 – 730.89). 13. Actinomycosis, only as an adjunct to conventional therapy when the disease process is refractory to antibiotics and surgical treatment (039.0 – 039.4, 039.8 – 039.9). Conditions for Review: 1. Selected problem wounds 2. Anaerobic septicemia (038.3) and infection other than clostridial (nonclostridial gas gangrene) 3. Acute thermal burns/radiation tissue injury (940 – 949). Conditions Not Medically Necessary: All other diagnosis not previously listed. Conditions Experimental/Investigational: 1. Multiple Sclerosis (340) 2. Topical Application of Oxygen (THBO) -- does not meet the definition of hyperbaric oxygen therapy as stated above. Also, its clinical efficacy has not been established. Therefore, use of topical oxygen is investigational and therefore non-covered. 3. Claims for Partial Body Hyperbaric Oxygen Therapy should be denied as investigational and therefore non-covered." Rationale section added In Coding section: Removed HCPCS Code: G0167 Added HCPCS Code: A4575 Removed Diagnosis Codes: 686.01, 987.9




Added Diagnosis Codes: 111.0-111.9, 112.0-112.3, 117.7, 117.9, 249.00-250.93, 285.1, 324.0, 362.31, 383.20-383.22, 443.89, 443.9, 459.9, 526.4, 595.82, 686.00-686.9, 707.00-707.19, 707.20-707.25, 707.8-707.9, 728.86, 728.9, 729.71-729.79, 903.01-903.9, 904.1, 904.51, 904.53, 904.6-904.9, 906.0-906.1, 906.4, 909.2, 941.20-941.59, 942.20-942.59, 943.20-943.59, 944.20-944.58, 945.20-945.59, 946.2-946.5, 948.00-948.99, 949.2-949.5, 958.8, 958.90-958.99, 998.83 References section updated

10-11-2011 In the Policy title, removed “(HBO2) Therapy” and inserted “Pressurization (HBO)” to read “Hyperbaric Oxygen Pressurization (HBO)” Updated the Description section. In the Policy section: • In Item A, #5, removed “(CRAO)” • In Item C, removed “all other conditions” and inserted “the following conditions” • In Item C, added the following conditions:

1. acute osteomyelitis, refractory to standard medical management; 2. acute surgical and traumatic wounds; 3. spinal cord injury; 4. traumatic brain injury; 5. severe or refractory Crohn’s disease; 6. acute brown recluse spider bites; 7. bone grafts; 8. carbon tetrachloride poisoning, acute; 9. cerebrovascular disease, acute (thrombotic or embolic) or chronic;

10. fracture healing; 11. hydrogen sulfide poisoning; 12. intra-abdominal abscesses; 13. lepromatous leprosy; 14. meningitis; 15. Pseudomembranous colitis (antimicrobial agent-induced colitis); 16. radiation myelitis; 17. sickle cell crisis and/or hematuria; 18. demyelinating diseases, e.g., multiple sclerosis, amyotrophic lateral sclerosis; 19. retinopathy, adjunct to scleral buckling procedures in patients with sickle cell

peripheral retinopathy and retinal detachment; 20. pyoderma gangrenosum; 21. acute coronary syndromes and as an adjunct to coronary interventions, including

but not limited to, percutaneous coronary interventions and cardiopulmonary bypass;

22. idiopathic sudden sensorineural hearing loss; 23. refractory mycoses: mucormycosis, actinomycosis, canidiobolus coronato; 24. cerebral edema, acute; 25. migraine; 26. in vitro fertilization; 27. cerebral palsy; 28. tumor sensitization for cancer treatments, including but not limited to,

radiotherapy or chemotherapy; 29. delayed onset muscle soreness; 30. idiopathic femoral neck necrosis; 31. chronic arm lymphedema following radiotherapy for cancer; 32. radiation-induced injury in the head and neck; 33. early treatment (beginning at completion of radiation therapy) to reduce adverse

effects of radiation therapy; and 34. autism spectrum disorders.”




Updated the Rationale section. Updated the References section.

01-01-2012 In the Coding section: Added HCPCS code A9272

01-30-2012 In the Coding section: Removed HCPCS code A9272

03-27-2014 In Policy section: In Item A, #3, added "e.g., crush injuries, reperfusion injury, compartment

syndrome" to read "Acute traumatic ischemia (e.g., crush injuries, reperfusion injury, compartment syndrome); or"

In Item A, removed #11, crush injuries was incorporated into Item A, #3. In Item C, added #36, "bisphosphonate-related osteonecrosis of the jaw" In Item C, added #37, "acute ischemic stroke; and" In Item C, added #38. "Bell's palsy." Rationale section updated. In Coding section: Added ICD-10 Diagnosis (Effective October 1, 2014) Reference section updated.

01-23-2015 In Policy title: Changed title from, "Hyperbaric Oxygen-Pressurization (HBO)" In Policy section: In Item A, #7, removed the word "treatments" and changed to "days" to read,

"Chronic non-healing wounds which have not responded to 30 days of appropriate conservative treatment and which show continued response when evaluated at 30 day intervals;"

Updated Rationale section. In Coding section: Added HCPCS code G0277. Removed HCPCS code C1300. Updated effective date for ICD-10 to October 1, 2015. Update References section.

02-05-2015 In Policy section: In Item C, removed wording "conditions, but limited to," and corrected to,

"Hyperbaric oxygen pressurization is considered experimental / investigational in the treatment of the following conditions including, but not limited to:"

11-12-2015 Updated Description section. In Policy section: In Item A 1, removed "when performed in accordance with Undersea and Hyperbaric

Medical Society (UHMS) guidelines". In Item A 4, added "acute" to read, "Carbon monoxide poisoning, acute;" In Item A 6, added "acute" to read, "Cyanide poisoning, acute;" Removed Item A 9 "Compartment syndrome," as this is stated in Item A 3. In Item A 13, added "acute" to read, "Gas or air embolism, acute;" In Item C, removed "in the treatment of the following conditions" and added "in all

other situations" to read, "Hyperbaric oxygen pressurization is considered experimental/investigational in all other situations including, but not limited to:"

In Item C 5, removed "severe or refractory Crohn's disease" and added "irritable bowel syndrome (Crohn's disease or ulcerative colitis)"

In Item C 32, added "(except as noted in Item A 11 above)" to read, "radiation-induced injury in the head and neck (except as noted in Item A 11 above);"

Added Items C 37-41. In Policy Guidelines, added section on Topical Hyperbaric Oxygen.




In Coding section: Revised nomenclature to CPT code 99183. Updated Rationale section. Updated References section.

11-19-2015 Updated References section of revision on 11-12-2015 ("In Policy Guidelines, added section on Topical Hyperbaric Oxygen.").

10-01-2016 In Coding section: Removed ICD-10 codes: A18.01, A18.03, A42.0, A42.1, A42.81, A42.82, A43.0,

E08.00, E08.01, E08.10, E08.11, E08.21, E08.22, E08.29, E08.311, E08.319, E08.36, E08.39, E08.40, E08.41, E08.42, E08.43, E08.44, E08.49, E08.51, E08.610, E08.618, E08.630, E08.638, E08.641, E08.649, E08.65, E08.69, E08.8, E08.9, E09.00, E09.01, E09.10, E09.11, E09.21, E09.22, E09.29, E09.311, E09.319, E09.36, E09.39, E09.40, E09.41, E09.42, E09.43, E09.44, E09.49, E09.51, E09.610, E09.618, E09.630, E09.638, E09.641, E09.649, E09.65, E09.69, E09.8, E09.9, E10.10, E10.11, E10.21, E10.22, E10.29, E10.311, E10.319, E10.36, E10.39, E10.40, 310.41, 310.42, E10.43, 310.44, E10.49, E10.51, E10.610, E10.618, E10.630, E10.638, E10.641, E10.649, E10.65, E10.69, E10.8, E10.9, E11.00, E11.01, E11.21, E11.22, E11.29, E11.311, E11.319, E11.36, E11.39, E11.40, E11.41, E11.42, E11.43, E11.44, E11.49, E11.51, E11.610, E11.618, E11.630, E11.638, E11.641, E11.649, E11.65, E11.69, E11.8, E11.9, E13.00, E13.01, E13.10, E13.11, E13.21, E13.22, E13.29, E13.311, E13.319, E13.36, E13.39, E13.40, E13.41, E13.42, E13.43, E13.44, E13.49, E13.51, E13.610, E13.618, E13.630, E13.638, E13.641, E13.649, E13.65, E13.69, E13.8, E13.9, E83.2

Termed ICD-10 codes effective 09-30-2016: E08.321, E08.329, E08.331, E08.339, E08.341, E08.349, E08.351, E08.359, E09.321, E09.329, E09.331, E09.339, E09.341, E09.349, E09.351, E09.359, E10.321, 310.329, 310.331, E10.339, E10.341, E10.349, E10.351, E10.359, E11.321, E11.329, E11, 331, E11.339, E11.341, E11.349, E11.351, E11.359, E13.321, E13.329, E13.331, E13.339, E13.341, E13.349, E13.351, E13.359

02-15-2017 Updated Description section. Updated Rationale section. In Coding section: Updated coding bullet. Updated References section.

10-01-2017 In Coding section: Added ICD-10 codes: L97.125, L97.126, L97.128, L97.215, L97.216, L97.218,

L97.225, L97.226, L97.228, L97.315, L97.316, L97.318, L97.325, L97.326, L97.328, L97.415, L97.416, L97.418, L97.425, L97.426, L97.428, L97.515, L97.516, L97.518, L97.525, L97.526, L97.528, L97.815, L97.816, L97.818, L97.825, L97.826, L97.828, L97.915, L97.916, L97.918, L97.925, L97.926, L97.928, L98.415, L98.416, L98.418, L98.425, L98.426, L98.428, L98.495, L98.496, L98.498

02-15-2018 Updated Description section. Updated Rationale section. In Coding section: Removed ICD-9 codes. Updated References section.

04-26-2019 The policy published to the bcbsks.com website on 03-27-2019 with an effective date of 04-26-2019. Updated Description section. In Policy section: Removed previous Item A 1, “Acute peripheral arterial insufficiency; OR”. Removed previous Item A 2, “Acute thermal burns: deep second degree or third

degree in nature; OR”. Removed previous Item A 5, “Central retinal artery occlusion; OR”.




In Item A 4 (previous Item A 7), removed “chronic” and “and which show continued response when evaluated at 30 day intervals” and added “diabetic” and “of the lower extremities in patients who meet the following criteria” to read, “Non-healing diabetic wounds of the lower extremities in patients who meet the following criteria”.

Added new Item A 4 a, “Patient has type 1 or type 2 diabetes and has a lower extremity wound due to diabetes”.

Added new Item A 4 b, “Patient has a wound classified as Wagner grade 3 or higher (see Policy Guidelines)”.

In Item A 5 (previous Item A 8), removed “(refractory osteomyelitis)” to read, “Chronic refractory osteomyelitis”.

Removed previous Item A 9, “Compromised skin graft or flaps (enhancement of healing in selected wounds); OR”.

In Item A 7 (previous Item A 11), removed “delayed radiation injury, including osteoradionecrosis” and “and radiation cystitis” to read, “Soft tissue radiation necrosis”.

In Item A 8 (previous Item A 12), removed “or air” to read, “Gas embolism, acute”. In Item A 9 (previous Item A 13), removed “myositis and” to read, “Gas gangrene (ie,

clostridial myonecrosis)”. Removed previous Item A 14, “Intracranial abscess; OR”. Removed previous Item A 15, “Necrotizing soft tissue infections; OR” In Item A 10 (previous Item A 16”, removed “prophylactic” and added “(non-

implanted related)” to read, “Pre and post treatment for individuals undergoing dental surgery (non-implant related) of an irradiated jaw”.

In Item A 11 (previous Item A 17), added “profound”, “only”, “blood”, and “must be” to read, “Profound anemia with exceptional blood loss: only when blood transfusion is impossible or must be delayed.”

In Item B, added “the treatment of the following conditions” to read, “Hyperbaric oxygen pressurization is considered experimental / investigational in all other situations including, but not limited to, the treatment of the following conditions:”.

In Item B 1, removed “refractory to standard medical management” to read, “Acute osteomyelitis”.

In Item B 5, removed “irritable” and “syndrome” and added “inflammatory” and “disease” to read, “Inflammatory bowel disease (Crohn’s disease or ulcerative colitis)”.

In Item B 12, added “and intracranial” to read, “Intra-abdominal and intracranial abscesses”.

Added new Item B 41, “Compromised skin grafts or flaps”. Added new Item B 42, “Necrotizing soft tissue infections”. Added new Item B 43, “Acute thermal burns”. Added new Item B 44, “Chronic wounds, other than those in patients with diabetes

who meet the criteria specified in Item A 4 above”. Added new Item B 45, “Acute arterial peripheral insufficiency”. In Item B 48 (previous Item B 43), removed “insufficiency, acute” and added “central”

and “occlusion” to read, “Central retinal artery occlusion.” Updated Policy Guidelines. Updated Rationale section. Updated References section.

06-19-2019 In Policy section: Policy Guidelines updated to include treatment session recommendations.

10-01-2019 In Coding section: Added ICD-10 Codes: L89.006, L89.016, L89.026, L89.106, L89.116, L89.126,

L89.136, L89.146, L89.156, L89.206, L89.216, L89.226, L89.306, L89.316, L89.326, L89.46, L89.506, L89.516, L89.526, L89.606, L89.616, L89.626, L89.816, L89.896, L89.96




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Other References 1. Blue Cross and Blue Shield of Kansas, Board of Directors meeting, May 17, 1990 (see Blue Cross and

Blue Shield of Kansas Newsletter, Blue Shield Report BS-3-90). 2. Blue Cross and Blue Shield of Kansas, Surgery Liaison Committee meeting, November 2, 1989 (see

Blue Cross and Blue Shield of Kansas Newsletter, Blue Shield Report BS-3-90). 3. Blue Cross and Blue Shield of Kansas Podiatry Liaison Committee Consent Ballot, March 2019. 4. Blue Cross and Blue Shield of Kansas Surgery Liaison Committee Consent Ballot, March 2019. 5. Blue Cross and Blue Shield of Kansas Podiatry Liaison Committee, January 2015; January 2018.

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Hyperbaric Oxygen Therapy (HBOT) - bcbsks.com … · 04/10/2019 · Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen at pressures between 1.5 and 3.0 atmospheres (atm)